Skip to main content

Notch Signaling in Thyroid Cancer

  • Chapter
  • First Online:
Notch Signaling in Embryology and Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1287))

Abstract

Thyroid cancer is the most common malignancy of the endocrine system with a steadily rising incidence. The term “thyroid cancer” encompasses a spectrum of subtypes, namely papillary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, and medullary thyroid cancer. Each subtype differs histopathologically and in degrees of cellular differentiation, which may be in part due to signaling of the Notch pathway. The Notch pathway is an evolutionarily conserved signal transduction mechanism that regulates cell proliferation, differentiation, survival, stem cell maintenance, embryonic and adult development, epithelial–mesenchymal transition, and angiogenesis. Its role in cancer biology is controversial, as it has been shown to play both an oncogenic and tumor-suppressive role in many different types of cancers. This discordance holds true for each subtype of thyroid cancer, indicating that Notch signaling is likely cell type and context dependent. Whether oncogenic or not, Notch signaling has proven to be significantly involved in the tumorigenesis of thyroid cancer and has thus earned interest as a therapeutic target. Advancement in the understanding of Notch signaling in thyroid cancer holds great promise for the development of novel treatment strategies to benefit patients.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adler JT, Hottinger DG, Kunnimalaiyaan M, Chen H (2010) Inhibition of growth in medullary thyroid cancer cells with histone deacetylase inhibitors and lithium chloride. J Surg Res 159(2):640–644. https://doi.org/10.1016/j.jss.2008.08.004. Epub 2008 Sep 4.

    Article  CAS  PubMed  Google Scholar 

  • Catalano MG, Fortunati N, Pugliese M, Costantino L, Poli R, Bosco O, Boccuzzi G (2005) Valproic acid induces apoptosis and cell cycle arrest in poorly differentiated thyroid cancer cells. J Clin Endocrinol Metab 90(3):1383–1389. Epub 2004 Dec 7.

    Article  CAS  Google Scholar 

  • Catalano MG, Fortunati N, Pugliese M, Poli R, Bosco O, Mastrocola R, Aragno M, Boccuzzi G (2006) Valproic acid, a histone deacetylase inhibitor, enhances sensitivity to doxorubicin in anaplastic thyroid cancer cells. J Endocrinol 191(2):465–472

    Article  CAS  Google Scholar 

  • Chen H, Thiagalingam A, Chopra H, Borges MW, Feder JN, Nelkin BD, Baylin SB, Ball DW (1997) Conservation of the Drosophila lateral inhibition pathway in human lung cancer: a hairy-related protein (HES-1) directly represses achaete-scute homolog-1 expression. Proc Natl Acad Sci U S A 94(10):5355–5360

    Article  CAS  Google Scholar 

  • Chen J, Tward JD, Shrieve DC, Hitchcock YJ (2008) Surgery and radiotherapy improve survival in patients with anaplastic thyroid carcinoma: analysis of the surveillance, epidemiology, and end results 1983-2002. Am J Clin Oncol 31(5):460–464. https://doi.org/10.1097/COC.0b013e31816a61f3

    Article  CAS  PubMed  Google Scholar 

  • Choi D, Ramu S, Park E, Jung E, Yang S, Jung W, Choi I, Lee S, Kim KE, Seong YJ, Hong M, Daghlian G, Kim D, Shin E, Seo JI, Khatchadourian V, Zou M, Li W, De Filippo R, Kokorowski P, Chang A, Kim S, Bertoni A, Furlanetto TW, Shin S, Li M, Chen Y, Wong A, Koh C, Geliebter J, Hong YK (2016) Aberrant activation of notch signaling inhibits PROX1 activity to enhance the malignant behavior of thyroid cancer cells. Cancer Res 76(3):582–593. https://doi.org/10.1158/0008-5472.CAN-15-1199. Epub 2015 Nov 25.

    Article  CAS  PubMed  Google Scholar 

  • Cook M, Yu XM, Chen H (2010) Notch in the development of thyroid C-cells and the treatment of medullary thyroid cancer. Am J Transl Res 2(1):119–125

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Sherman S, Tuttle RM, American Thyroid Association Guidelines Taskforce (2006) Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 16(2):109–142

    Article  Google Scholar 

  • Damaskos C, Garmpis N, Valsami S, Spartalis E, Antoniou EA, Tomos P, Karamaroudis S, Zoumpou T, Pergialiotis V, Stergios K, Michaelides C, Kontzoglou K, Perrea D, Nikiteas N, Dimitroulis D (2016) Histone deacetylase inhibitors: a novel therapeutic weapon against medullary thyroid cancer? Anticancer Res 36(10):5019–5024

    Article  CAS  Google Scholar 

  • Dantas-Barbosa C, Bergthold G, Daudigeos-Dubus E, Blockus H, Boylan JF, Ferreira C, Puget S, Abely M, Vassal G, Grill J, Geoerger B (2015) Inhibition of the NOTCH pathway using γ-secretase inhibitor RO4929097 has limited antitumor activity in established glial tumors. Anti-Cancer Drugs 26(3):272–283. https://doi.org/10.1097/CAD.0000000000000190

    Article  CAS  PubMed  Google Scholar 

  • Dexter JS (1914) The analysis of a case of continuous variation in Drosophila by a study of its linkage relations. Am Nat 576(48):712–758

    Article  Google Scholar 

  • Ellisen L, Bird J, West D, Soreng A, Reynolds T, Smith S et al (1991) TAN-1, the human homolog of the drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell 66:649–661. https://doi.org/10.1016/0092-8674(91)90111-B

    Article  CAS  PubMed  Google Scholar 

  • Erba E, Bergamaschi D, Ronzoni S, Faretta M, Taverna S, Bonfanti M, Catapano CV, Faircloth G, Jimeno J, D’Incalci M (1999) Mode of action of thiocoraline, a natural marine compound with anti-tumour activity. Br J Cancer 80(7):971–980

    Article  CAS  Google Scholar 

  • Fabbri G, Rasi S, Rossi D et al (2011) Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation. J Exp Med 208(7):1389–1401. https://doi.org/10.1084/jem.20110921

  • Ferretti E, Tosi E, Po A, Scipioni A, Morisi R, Espinola MS, Russo D, Durante C, Schlumberger M, Screpanti I, Filetti S, Gulino A (2008) Notch signaling is involved in expression of thyrocyte differentiation markers and is down-regulated in thyroid tumors. J Clin Endocrinol Metab 93(10):4080–4087. https://doi.org/10.1210/jc.2008-0528. Epub 2008 Jul 29.

    Article  CAS  PubMed  Google Scholar 

  • Fortunati N, Catalano MG, Arena K, Brignardello E, Piovesan A, Boccuzzi G (2004) Valproic acid induces the expression of the Na+/I- symporter and iodine uptake in poorly differentiated thyroid cancer cells. J Clin Endocrinol Metab 89(2):1006–1009

    Article  CAS  Google Scholar 

  • Furuya-Kanamori L, Bell KJL, Clark J, Glasziou P, Doi SAR (2016) Prevalence of differentiated thyroid cancer in autopsy studies over six decades: a meta-analysis. J Clin Oncol 34(30):3672–3679. https://doi.org/10.1200/JCO.2016.67.7419

    Article  PubMed  Google Scholar 

  • Gallo C, Fragliasso V, Donati B, Torricelli F, Tameni A, Piana S, Ciarrocchi A (2018) The bHLH transcription factor DEC1 promotes thyroid cancer aggressiveness by the interplay with NOTCH1. Cell Death Dis 9(9):871. https://doi.org/10.1038/s41419-018-0933-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geers C, Colin IM, Gérard AC. Delta-like 4/Notch pathway is differentially regulated in benign and malignant thyroid tissues. Thyroid 21(12):1323–1330. https://doi.org/10.1089/thy.2010.0444. Epub 2011 Nov 8.

  • Greenblatt DY, Chen H (2007) Palliation of advanced thyroid malignancies. Surg Oncol 16(4):237–247. Epub 2007 Sep 14.

    Article  Google Scholar 

  • Greenblatt DY, Cayo MA, Adler JT, Ning L, Haymart MR, Kunnimalaiyaan M, Chen H (2008) Valproic acid activates Notch1 signaling and induces apoptosis in medullary thyroid cancer cells. Ann Surg 247(6):1036–1040. https://doi.org/10.1097/SLA.0b013e3181758d0e

    Article  PubMed  PubMed Central  Google Scholar 

  • Grüning T, Tiepolt C, Zöphel K, Bredow J, Kropp J, Franke WG (2003) Retinoic acid for redifferentiation of thyroid cancer–does it hold its promise? Eur J Endocrinol 148(4):395–402

    Article  Google Scholar 

  • Grünwald F, Pakos E, Bender H, Menzel C, Otte R, Palmedo H, Pfeifer U, Biersack HJ (1998) Redifferentiation therapy with retinoic acid in follicular thyroid cancer. J Nucl Med 39(9):1555–1558

    PubMed  Google Scholar 

  • Guruharsha KG, Kankel MW, Artavanis-Tsakonas S (2012) The notch signalling system: recent insights into the complexity of a conserved pathway. Nat Rev Genet 13(9):654–666. https://doi.org/10.1038/nrg3272. Epub 2012 Aug 7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hanlon L, Avila JL, Demarest RM, Troutman S, Allen M, Ratti F, Rustgi AK, Stanger BZ, Radtke F, Adsay V, Long F, Capobianco AJ, Kissil JL (2010) Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma. Cancer Res 70(11):4280–4286. https://doi.org/10.1158/0008-5472.CAN-09-4645

  • Hsu KT, Yu XM, Audhya AW, Jaume JC, Lloyd RV, Miyamoto S, Prolla TA, Chen H (2014) Novel approaches in anaplastic thyroid cancer therapy. Oncologist 19(11):1148–1155. https://doi.org/10.1634/theoncologist.2014-0182. Epub 2014 Sep 26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jang S, Yu XM, Odorico S, Clark M, Jaskula-Sztul R, Schienebeck CM, Kupcho KR, Harrison AD, Winston-McPherson GN, Tang W, Chen H (2015) Novel analogs targeting histone deacetylase suppress aggressive thyroid cancer cell growth and induce re-differentiation. Cancer Gene Ther 22(8):410–416. https://doi.org/10.1038/cgt.2015.37. Epub 2015 Aug 7.

    Article  CAS  PubMed  Google Scholar 

  • Jaskula-Sztul R, Pisarnturakit P, Landowski M, Chen H, Kunnimalaiyaan M (2011) Expression of the active Notch1 decreases MTC tumor growth in vivo. J Surg Res 171(1):23–27. https://doi.org/10.1016/j.jss.2011.03.035. Epub 2011 Apr 13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jin S, Borkhuu O, Bao W, Yang YT (2016) Signaling pathways in thyroid cancer and their therapeutic implications. J Clin Med Res 8(4):284–296. https://doi.org/10.14740/jocmr2480w. Epub 2016 Feb 27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jung CW, Kong JS, Seol H, Park S, Koh JS, Lee SS, Kim MJ, Choi IJ, Myung JK (2017) Expression of activated Notch1 and Hey1 in papillary thyroid carcinoma. Histopathology 70(2):301–308. https://doi.org/10.1111/his.13065. Epub 2016 Nov 2.

  • Kelly WK, O’Connor OA, Krug LM, Chiao JH, Heaney M, Curley T, MacGregore-Cortelli B, Tong W, Secrist JP, Schwartz L, Richardson S, Chu E, Olgac S, Marks PA, Scher H, Richon VM (2005) Phase I study of an oral histone deacetylase inhibitor, suberoylanilide hydroxamic acid, in patients with advanced cancer. J Clin Oncol 23(17):3923–3931. Epub 2005 May 16.

    Article  CAS  Google Scholar 

  • Kim HJ, Kim MJ, Kim A, Jung CW, Park S, Koh JS, Myung JK (2017) The role of Notch1 signaling in anaplastic thyroid carcinoma. Canacer Res Treat 49(2):509–517. https://doi.org/10.4143/crt.2016.214. Epub 2016 Sep 1.

    Article  CAS  Google Scholar 

  • Klinakis A, Lobry C, Abdel-Wahab O, Oh P, Haeno H, Buonamici S, van De Walle I, Cathelin S, Trimarchi T, Araldi E, Liu C, Ibrahim S, Beran M, Zavadil J, Efstratiadis A, Taghon T, Michor F, Levine RL, Aifantis I (2011) A novel tumour-suppressor function for the Notch pathway in myeloid leukaemia. Nature 473(7346):230–233. https://doi.org/10.1038/nature09999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kogai T, Taki K, Brent GA (2006) Enhancement of sodium/iodide symporter expression in thyroid and breast cancer. Endocr Relat Cancer 13(3):797–826

    Article  CAS  Google Scholar 

  • Kunnimalaiyaan M, Traeger K, Chen H (2005) Conservation of the Notch1 signaling pathway in gastrointestinal carcinoid cells. Am J Physiol Gastrointest Liver Physiol 289(4):G636–G642

    Article  CAS  Google Scholar 

  • Kunnimalaiyaan M, Vaccaro AM, Ndiaye MA, Chen H (2006) Overexpression of the NOTCH1 intracellular domain inhibits cell proliferation and alters the neuroendocrine phenotype of medullary thyroid cancer cells. J Biol Chem 281(52):39819–39830. Epub 2006 Nov 7.

    Article  CAS  Google Scholar 

  • Lin JD, Chao TC, Hsueh C (2004) Follicular thyroid carcinomas with lung metastases: a 23-year retrospective study. Endocr J 51(2):219–225

    Article  Google Scholar 

  • Lobry C, Oh P, Aifantis I (2011) Oncogenic and tumor suppressor functions of notch in cancer: it’s NOTCH what you think. J Exp Med 208(10):1931–1935. https://doi.org/10.1084/jem.20111855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lou I, Odorico S, Yu XM, Harrison A, Jaskula-Sztul R, Chen H (2018) Notch3 as a novel therapeutic target in metastatic medullary thyroid cancer. Surgery 163(1):104–111. https://doi.org/10.1016/j.surg.2017.07.039. Epub 2017 Nov 8.

    Article  PubMed  Google Scholar 

  • Mao Y, Xing M (2016) Recent incidences and differential trends of thyroid cancer in the USA. Endocr Relat Cancer 23(4):313–322. https://doi.org/10.1530/ERC-15-0445. Epub 2016 Feb 25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Messersmith WA, Shapiro GI, Cleary JM, Jimeno A, Dasari A, Huang B, Shaik MN, Cesari R, Zheng X, Reynolds JM, English PA, McLachlan KR, Kern KA, LoRusso PM (2015) A phase I, dose-finding study in patients with advanced solid malignancies of the oral γ-secretase inhibitor PF-03084014. Clin Cancer Res 21(1):60–67. https://doi.org/10.1158/1078-0432.CCR-14-0607. Epub 2014 Sep 17.

    Article  CAS  PubMed  Google Scholar 

  • Mohr OL (1919) Character changes caused by mutation of an entire region of a chromosome in Drosophila. Genetics 4:275–232

    CAS  PubMed  PubMed Central  Google Scholar 

  • Morimura T, Goitsuka R, Zhang Y, Saito I, Reth M, Kitamura D (2000) Cell cycle arrest and apoptosis induced by Notch1 in B cells. J Biol Chem 275(47):36523–36531

    Article  CAS  Google Scholar 

  • Morris LGT, Sikora AG, Tosteson TD, Davies L (2013) The increasing incidence of thyroid cancer: the influence of access to care. Thyroid 23(7):885–891. https://doi.org/10.1089/thy.2013.0045. Epub 2013 Apr 18.

    Article  PubMed  PubMed Central  Google Scholar 

  • Nakakura EK, Sriuranpong VR, Kunnimalaiyaan M, Hsiao EC, Schuebel KE, Borges MW, Jin N, Collins BJ, Nelkin BD, Chen H, Ball DW (2005) Regulation of neuroendocrine differentiation in gastrointestinal carcinoid tumor cells by notch signaling. J Clin Endocrinol Metab 90(7):4350–4356. Epub 2005 May 3.

    Article  CAS  Google Scholar 

  • Negri A, Marco E, García-Hernández V, Domingo A, Llamas-Saiz AL, Porto-Sandá S et al (2007) Antitumor activity, X-ray crystal structure, and DNA binding properties of thiocoraline a, a natural bisintercalating thiodepsipeptide. J Med Chem 50:3322–3333

    Article  CAS  Google Scholar 

  • Nickoloff BJ, Qin JZ, Chaturvedi V, Denning MF, Bonish B, Miele L (2002) Jagged-1 mediated activation of notch signaling induces complete maturation of human keratinocytes through NF-kappaB and PPARgamma. Cell Death Differ 9(8):842–855

    Article  CAS  Google Scholar 

  • Nilubol N, Merkel R, Yang L, Patel D, Reynolds JC, Sadowski SM, Neychev V, Kebebew E (2017) A phase II trial of valproic acid in patients with advanced, radioiodine-resistant thyroid cancers of follicular cell origin. Clin Endocrinol 86(1):128–133. https://doi.org/10.1111/cen.13154. Epub 2016 Sep 8.

    Article  CAS  Google Scholar 

  • Ning L, Greenblatt DY, Kunnimalaiyaan M, Chen H (2008) Suberoyl bis-hydroxamic acid activates Notch-1 signaling and induces apoptosis in medullary thyroid carcinoma cells. Oncologist 13(2):98–104. https://doi.org/10.1634/theoncologist.2007-0190

    Article  CAS  PubMed  Google Scholar 

  • Patel PN, Yu XM, Jaskula-Sztul R, Chen H (2014) Hesperetin activates the Notch1 signaling cascade, causes apoptosis, and induces cellular differentiation in anaplastic thyroid cancer. Ann Surg Oncol 21 Suppl 4(0 4):S497–S504. https://doi.org/10.1245/s10434-013-3459-7

    Article  PubMed  Google Scholar 

  • Piana S, Zanetti E, Bisagni A, Ciarrocchi A, Giordano D, Torricelli F, Rossi T, Ragazzi M (2019) Expression of NOTCH1 in thyroid cancer is mostly restricted to papillary carcinoma. Endocr Connect 8(8):1089–1096. https://doi.org/10.1530/EC-19-0303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Powers AE, Marcadis AR, Lee M, Morris LGT, Marti JL (2019) Changes in trends in thyroid cancer incidence in the United States, 1992 to 2016. JAMA 322(24):2440–2441. https://doi.org/10.1001/jama.2019.18528

    Article  PubMed  PubMed Central  Google Scholar 

  • Puente XS, Pinyol M, Quesada V, Conde L, Ordóñez GR, Villamor N, Escaramis G, Jares P, Beà S, González-Díaz M, Bassaganyas L, Baumann T, Juan M, López-Guerra M, Colomer D, Tubío JM, López C, Navarro A, Tornador C, Aymerich M, Rozman M, Hernández JM, Puente DA, Freije JM, Velasco G, Gutiérrez-Fernández A, Costa D, Carrió A, Guijarro S, Enjuanes A, Hernández L, Yagüe J, Nicolás P, Romeo-Casabona CM, Himmelbauer H, Castillo E, Dohm JC, de Sanjosé S, Piris MA, de Alava E, San Miguel J, Royo R, Gelpí JL, Torrents D, Orozco M, Pisano DG, Valencia A, Guigó R, Bayés M, Heath S, Gut M, Klatt P, Marshall J, Raine K, Stebbings LA, Futreal PA, Stratton MR, Campbell PJ, Gut I, López-Guillermo A, Estivill X, Montserrat E, López-Otín C, Campo E (2011) Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature 475(7354):101–105. https://doi.org/10.1038/nature10113

  • Qi R, An H, Yu Y, Zhang M, Liu S, Xu H, Guo Z, Cheng T, Cao X (2003) Notch1 signaling inhibits growth of human hepatocellular carcinoma through induction of cell cycle arrest and apoptosis. Cancer Res 63(23):8323–8329

    CAS  PubMed  Google Scholar 

  • Ragazzi M, Ciarrocchi A, Sancisi V, Gandolfi G, Bisagni A, Piana S (2014) Update on anaplastic thyroid carcinoma: morphological, molecular, and genetic features of the most aggressive thyroid cancer. Int J Endocrinol 2014:790834. https://doi.org/10.1155/2014/790834. Epub 2014 Aug 21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rangarajan A, Talora C, Okuyama R, Nicolas M, Mammucari C, Oh H, Aster JC, Krishna S, Metzger D, Chambon P, Miele L, Aguet M, Radtke F, Dotto GP (2001) Notch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation. EMBO J 20(13):3427–3436

    Article  CAS  Google Scholar 

  • Rashid FA, Mansoor Q, Tabassum S, Aziz H, Arfat WO, Naoum GE, Ismail M, Farooqi AA (2018) Signaling cascades in thyroid cancer: increasing the armory of archers to hit Bullseye. J Cell Biochem 119(5):3798–3808. https://doi.org/10.1002/jcb.26620. Epub 2018 Jan 22.

    Article  CAS  PubMed  Google Scholar 

  • Reedijk M, Odorcic S, Chang L, Zhang H, Miller N, McCready DR, Lockwood G, Egan SE (2005) High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival. Cancer Res 65(18):8530–8537

    Article  CAS  Google Scholar 

  • Romero F, Espliego F, Pérez Baz J, García de Quesada T, Grávalos D, De la Calle F et al (1997) Thiocoraline, a new depsipeptide with antitumor activity produced by a marine Micromonospora. I. Taxonomy, fermentation, isolation, and biological activities. J Antibiot 50:734–737

    Article  CAS  Google Scholar 

  • Roy M, Chen H, Sippel RS (2013) Current understanding and management of medullary thyroid cancer. Oncologist 18(10):1093–1100. https://doi.org/10.1634/theoncologist.2013-0053. Epub 2013 Sep 13.

    Article  PubMed  PubMed Central  Google Scholar 

  • Schlumberger MJ (1998) Papillary and follicular thyroid carcinoma. N Engl J Med 338(5):297–306

    Article  CAS  Google Scholar 

  • Schmutzler C, Winzer R, Meissner-Weigl J, Köhrle J (1997) Retinoic acid increases sodium/iodide symporter mRNA levels in human thyroid cancer cell lines and suppresses expression of functional symporter in nontransformed FRTL-5 rat thyroid cells. Biochem Biophys Res Commun 240(3):832–838

    Article  CAS  Google Scholar 

  • Schneider DF, Chen H (2013) New developments in the diagnosis and treatment of thyroid cancer. CA Cancer J Clin 63(6):374–394. https://doi.org/10.3322/caac.21195. Epub 2013 Jun 24.

    Article  PubMed  Google Scholar 

  • Seib CD, Sosa JA (2019) Evolving understanding of the epidemiology of thyroid cancer. Endocrinol Metab Clin N Am 48(1):23–35. https://doi.org/10.1016/j.ecl.2018.10.002. Epub 2018 Dec 23.

    Article  Google Scholar 

  • Shen WT, Wong TS, Chung WY, Wong MG, Kebebew E, Duh QY, Clark OH (2005) Valproic acid inhibits growth, induces apoptosis, and modulates apoptosis-regulatory and differentiation gene expression in human thyroid cancer cells. Surgery 138(6):979–984; discussion 984–5.

    Article  Google Scholar 

  • Sherman EJ, Su YB, Lyall A, Schöder H, Fury MG, Ghossein RA, Haque S, Lisa D, Shaha AR, Tuttle RM, Pfister DG (2013) Evaluation of romidepsin for clinical activity and radioactive iodine reuptake in radioactive iodine-refractory thyroid carcinoma. Thyroid 23(5):593–599. https://doi.org/10.1089/thy.2012.0393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shou J, Ross S, Koeppen H, de Sauvage FJ, Gao WQ (2001) Dynamics of notch expression during murine prostate development and tumorigenesis. Cancer Res 61(19):7291–7297

    CAS  PubMed  Google Scholar 

  • Sikandar SS, Pate KT, Anderson S, Dizon D, Edwards RA, Waterman ML, Lipkin SM (2010) NOTCH signaling is required for formation and self-renewal of tumor-initiating cells and for repression of secretory cell differentiation in colon cancer. Cancer Res 70(4):1469–1478. https://doi.org/10.1158/0008-5472.CAN-09-2557. Epub 2010 Feb 9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sjölund J, Johansson M, Manna S, Norin C, Pietras A, Beckman S, Nilsson E, Ljungberg B, Axelson H (2008) Suppression of renal cell carcinoma growth by inhibition of Notch signaling in vitro and in vivo. J Clin Invest 118(1):217–228

    Article  Google Scholar 

  • Smallridge RC, Copland JA (2010) Anaplastic thyroid carcinoma: pathogenesis and emerging therapies. Clin Oncol (R Coll Radiol) 22(6):486–497. https://doi.org/10.1016/j.clon.2010.03.013. Epub 2010 Apr 24.

    Article  CAS  Google Scholar 

  • Somnay YR, Yu XM, Lloyd RV, Leverson G, Aburjania Z, Jang S, Jaskula-Sztul R, Chen H (2017) Notch3 expression correlates with thyroid cancer differentiation, induces apoptosis, and predicts disease prognosis. Cancer 123(5):769–782. https://doi.org/10.1002/cncr.30403. Epub 2016 Nov 2.

    Article  CAS  PubMed  Google Scholar 

  • Spartalis E, Athanasiadis DI, Chrysikos D, Spartalis M, Boutzios G, Schizas D, Garmpis N, Damaskos C, Paschou SA, Ioannidis A, Tsourouflis G, Dimitroulis D, Nikiteas NI (2019) Histone deacetylase inhibitors and anaplastic thyroid carcinoma. Anticancer Res 39(3):1119–1127. https://doi.org/10.21873/anticanres.13220

    Article  CAS  PubMed  Google Scholar 

  • Sriuranpong V, Borges MW, Ravi RK, Arnold DR, Nelkin BD, Baylin SB, Ball DW (2001) Notch signaling induces cell cycle arrest in small cell lung cancer cells. Cancer Res 61(7):3200–3205

    CAS  PubMed  Google Scholar 

  • Sriuranpong V, Borges MW, Strock CL, Nakakura EK, Watkins DN, Blaumueller CM, Nelkin BD, Ball DW (2002) Notch signaling induces rapid degradation of achaete-scute homolog 1. Mol Cell Biol 22(9):3129–3139

    Article  CAS  Google Scholar 

  • Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, Kryukov GV, Lawrence MS, Sougnez C, McKenna A, Shefler E, Ramos AH, Stojanov P, Carter SL, Voet D, Cortés ML, Auclair D, Berger MF, Saksena G, Guiducci C, Onofrio RC, Parkin M, Romkes M, Weissfeld JL, Seethala RR, Wang L, Rangel-Escareño C, Fernandez-Lopez JC, Hidalgo-Miranda A, Melendez-Zajgla J, Winckler W, Ardlie K, Gabriel SB, Meyerson M, Lander ES, Getz G, Golub TR, Garraway LA, Grandis JR (2011) The mutational landscape of head and neck squamous cell carcinoma. Science 333(6046):1157–1160. https://doi.org/10.1126/science.1208130. Epub 2011 Jul 28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sueda R, Imayoshi I, Harima Y, Kageyama R (2019) High Hes1 expression and resultant Ascl1 suppression regulate quiescent vs. active neural stem cells in the adult mouse brain. Genes Dev 33(9–10):511–523. https://doi.org/10.1101/gad.323196.118. Epub 2019 Mar 12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Talora C, Sgroi DC, Crum CP, Dotto GP (2002) Specific down-modulation of Notch1 signaling in cervical cancer cells is required for sustained HPV-E6/E7 expression and late steps of malignant transformation. Genes Dev 16(17):2252–2263

    Article  CAS  Google Scholar 

  • Takebe N, Nguyen D, Yang SX (2014) Targeting notch signaling pathway in cancer: clinical development advances and challenges. Pharmacol Ther 141(2):140–149. https://doi.org/10.1016/j.pharmthera.2013.09.005. Epub 2013 Sep 27.

  • Tesfazghi S, Eide J, Dammalapati A, Korlesky C, Wyche TP, Bugni TS, Chen H, Jaskula-Sztul R (2013) Thiocoraline alters neuroendocrine phenotype and activates the notch pathway in MTC-TT cell line. Cancer Med 2(5):734–743. https://doi.org/10.1002/cam4.118. Epub 2013 Sep 17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Truong M, Cook MR, Pinchot SN, Kunnimalaiyaan M, Chen H (2011) Resveratrol induces Notch2-mediated apoptosis and suppression of neuroendocrine markers in medullary thyroid cancer. Ann Surg Oncol 18(5):1506–1511. https://doi.org/10.1245/s10434-010-1488-z. Epub 2010 Dec 24.

    Article  PubMed  Google Scholar 

  • Viatour P, Ehmer U, Saddic LA, Dorrell C, Andersen JB, Lin C, Zmoos AF, Mazur PK, Schaffer BE, Ostermeier A, Vogel H, Sylvester KG, Thorgeirsson SS, Grompe M, Sage J (2011) Notch signaling inhibits hepatocellular carcinoma following inactivation of the RB pathway. J Exp Med 208(10):1963–1976. https://doi.org/10.1084/jem.20110198. Epub 2011 Aug 29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Westhoff B, Colaluca IN, D’Ario G, Donzelli M, Tosoni D, Volorio S, Pelosi G, Spaggiari L, Mazzarol G, Viale G, Pece S, Di Fiore PP (2009) Alterations of the Notch pathway in lung cancer. Proc Natl Acad Sci U S A 106(52):22293–22298. https://doi.org/10.1073/pnas.0907781106. Epub 2009 Dec 10.

  • Woyach JA, Kloos RT, Ringel MD, Arbogast D, Collamore M, Zwiebel JA, Grever M, Villalona-Calero M, Shah MH (2009) Lack of therapeutic effect of the histone deacetylase inhibitor vorinostat in patients with metastatic radioiodine-refractory thyroid carcinoma. J Clin Endocrinol Metab 94(1):164–170. https://doi.org/10.1210/jc.2008-1631. Epub 2008 Oct 14.

    Article  CAS  PubMed  Google Scholar 

  • Wu Y, Cain-Hom C, Choy L, Hagenbeek TJ, de Leon GP, Chen Y, Finkle D, Venook R, Wu X, Ridgway J, Schahin-Reed D, Dow GJ, Shelton A, Stawicki S, Watts RJ, Zhang J, Choy R, Howard P, Kadyk L, Yan M, Zha J, Callahan CA, Hymowitz SG, Siebel CW (2010) Therapeutic antibody targeting of individual notch receptors. Nature 464(7291):1052–1057. https://doi.org/10.1038/nature08878

    Article  CAS  PubMed  Google Scholar 

  • Wyche TP, Dammalapati A, Cho H, Harrison AD, Kwon GS, Chen H, Bugni TS, Jaskula-Sztul R (2014) Thiocoraline activates the Notch pathway in carcinoids and reduces tumor progression in vivo. Cancer Gene Ther 21(12):518–525. https://doi.org/10.1038/cgt.2014.57. Epub 2014 Nov 21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiao X, Ning L, Chen H (2009) Notch1 mediates growth suppression of papillary and follicular thyroid cancer cells by histone deacetylase inhibitors. Mol Cancer Ther 8(2):350–356. https://doi.org/10.1158/1535-7163.MCT-08-0585. Epub 2009 Feb 3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamashita AS, Geraldo MV, Fuziwara CS, Kulcsar MA, Friguglietti CU, da Costa RB, Baia GS, Kimura ET (2013) Notch pathway is activated by MAPK signaling and influences papillary thyroid cancer proliferation. Transl Oncol 6(2):197–205. https://doi.org/10.1593/tlo.12442. Epub 2013 Apr 1.

  • Yu XM, Phan T, Patel PN, Jaskula-Sztul R, Chen H (2013a) Chrysin activates Notch1 signaling and suppresses tumor growth of anaplastic thyroid carcinoma in vitro and in vivo. Cancer 119(4):774–781. https://doi.org/10.1002/cncr.27742. Epub 2012 Sep 18.

    Article  CAS  PubMed  Google Scholar 

  • Yu XM, Jaskula-Sztul R, Ahmed K, Harrison AD, Kunnimalaiyaan M, Chen H (2013b) Resveratrol induces differentiation markers expression in anaplastic thyroid carcinoma via activation of Notch1 signaling and suppresses cell growth. Mol Cancer Ther 12(7):1276–1287. https://doi.org/10.1158/1535-7163.MCT-12-0841.

  • Yu XM, Jaskula-Sztul R, Georgen MR, Aburjania Z, Somnay YR, Leverson G, Sippel RS, Lloyd RV, Johnson BP, Chen H (2016) Notch1 signaling regulates the aggressiveness of differentiated thyroid cancer and inhibits SERPINE1 expression. Clin Cancer Res 22(14):3582–3592. https://doi.org/10.1158/1078-0432.CCR-15-1749. Epub 2016 Feb 4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan L, Ma L, Xue H, Song S (2019) Relationship between the upregulation of Notch1 signaling and the clinical characteristics of patients with papillary thyroid carcinoma in East Asia: a systematic review and meta-analysis. Cancer Cell Int 19:5. https://doi.org/10.1186/s12935-018-0723-8. eCollection 2019.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zage PE, Nolo R, Fang W, Stewart J, Garcia-Manero G, Zweidler-McKay PA (2012) Notch pathway activation induces neuroblastoma tumor cell growth arrest. Pediatr Blood Cancer 58:682–689

    Article  Google Scholar 

  • Zhang M, Qin Y, Zuo B, Gong W, Zhang S, Gong Y, Quan Z, Chu B (2017) Overexpression of NOTCH-regulated Ankyrin Repeat Protein is associated with papillary thyroid carcinoma progression. PLoS One 12(2):e0167782. https://doi.org/10.1371/journal.pone.0167782

  • Zweidler-McKay PA, He Y, Xu L, Rodriguez CG, Karnell FG, Carpenter AC, Aster JC, Allman D, Pear WS (2005) Notch signaling is a potent inducer of growth arrest and apoptosis in a wide range of B-cell malignancies. Blood 106(12):3898–3906. Epub 2005 Aug 23.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Herbert Chen .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Guenter, R., Patel, Z., Chen, H. (2021). Notch Signaling in Thyroid Cancer. In: Reichrath, J., Reichrath, S. (eds) Notch Signaling in Embryology and Cancer. Advances in Experimental Medicine and Biology, vol 1287. Springer, Cham. https://doi.org/10.1007/978-3-030-55031-8_10

Download citation

Publish with us

Policies and ethics