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NOTCH and Esophageal Squamous Cell Carcinoma

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Book cover Notch Signaling in Embryology and Cancer

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

Abstract

Esophageal squamous cell carcinoma (ESCC) is a deadly disease that requires extensive research on its mechanisms, prevention, and therapy. Recent studies have shown that NOTCH mutations are commonly seen in human ESCC. This chapter summarizes our current understanding of the NOTCH pathway in normal esophagus and in ESCC. In normal esophagus, NOTCH pathway regulates the development of esophageal squamous epithelium, in particular, squamous differentiation. Exposure to extrinsic and intrinsic factors, such as gastroesophageal reflux, alcohol drinking, and inflammation, downregulates the NOTCH pathway and thus inhibits squamous differentiation of esophageal squamous epithelial cells. In ESCC, NOTCH plays a dual role as both a tumor suppressor pathway and an oncogenic pathway. In summary, further studies are warranted to develop NOTCH activators for the prevention of ESCC and NOTCH inhibitors for targeted therapy of a subset of ESCC with activated NOTCH pathway.

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Abbreviations

4NQO:

4-nitroquinoline 1-oxide

BE:

Barrett’s esophagus

ESCC:

esophageal squamous cell carcinoma

HNSCC:

head and neck squamous cell carcinoma

SCC:

squamous cell carcinoma

References

  • Agrawal N, Jiao Y, Bettegowda C, Hutfless SM, Wang Y, David S et al (2012) Comparative genomic analysis of esophageal adenocarcinoma and squamous cell carcinoma. Cancer Discov 2(10):899–905. PubMed PMID: 22877736. Pubmed Central PMCID: 3473124. Epub 2012/08/11. eng

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Al Labban D, Jo SH, Ostano P, Saglietti C, Bongiovanni M, Panizzon R et al (2018) Notch-effector CSL promotes squamous cell carcinoma by repressing histone demethylase KDM6B. J Clin Invest 128(6):2581–2599. PubMed PMID: 29757189. Pubmed Central PMCID: 5983322

    Article  PubMed  PubMed Central  Google Scholar 

  • Alcolea MP, Greulich P, Wabik A, Frede J, Simons BD, Jones PH (2014) Differentiation imbalance in single oesophageal progenitor cells causes clonal immortalization and field change. Nat Cell Biol 16(6):615–622. PubMed PMID: 24814514. Pubmed Central PMCID: 4085550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blanpain C, Lowry WE, Pasolli HA, Fuchs E (2006) Canonical notch signaling functions as a commitment switch in the epidermal lineage. Genes Dev 20(21):3022–3035. PubMed PMID: 17079689. Pubmed Central PMCID: 1620020. Epub 2006/11/03. eng

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Borggrefe T, Oswald F (2009) The Notch signaling pathway: transcriptional regulation at Notch target genes. Cell Mol Life Sci 66(10):1631–1646. PubMed PMID: 19165418. Epub 2009/01/24. eng

    Article  CAS  PubMed  Google Scholar 

  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424. PubMed PMID: 30207593

    Article  PubMed  Google Scholar 

  • Chang J, Tan W, Ling Z, Xi R, Shao M, Chen M et al (2017) Genomic analysis of oesophageal squamous-cell carcinoma identifies alcohol drinking-related mutation signature and genomic alterations. Nat Commun 8:15290. PubMed PMID: 28548104. Pubmed Central PMCID: 5477513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chanock SJ (2018) The paradox of mutations and cancer. Science 362(6417):893–894. PubMed PMID: 30467157

    Article  CAS  PubMed  Google Scholar 

  • Chen H, Fang Y, Tevebaugh W, Orlando RC, Shaheen NJ, Chen X (2011) Molecular mechanisms of Barrett’s esophagus. Dig Dis Sci 56(12):3405–3420. PubMed PMID: 21984436. Pubmed Central PMCID: 3750118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen H, Li J, Li H, Hu Y, Tevebaugh W, Yamamoto M et al (2012) Transcript profiling identifies dynamic gene expression patterns and an important role for Nrf2/Keap1 pathway in the developing mouse esophagus. PLoS One 7(5):e36504. PubMed PMID: 22567161. Pubmed Central PMCID: 3342176. Epub 2012/05/09. eng

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng C, Cui H, Zhang L, Jia Z, Song B, Wang F et al (2016) Genomic analyses reveal FAM84B and the NOTCH pathway are associated with the progression of esophageal squamous cell carcinoma. GigaScience 5:1. PubMed PMID: 26759717. Pubmed Central PMCID: 4709967

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ciccarelli FD (2019) Mutations differ in normal and cancer cells of the oesophagus. Nature 565(7739):301–303. PubMed PMID: 30643303

    Article  CAS  PubMed  Google Scholar 

  • Demehri S, Turkoz A, Kopan R (2009) Epidermal Notch1 loss promotes skin tumorigenesis by impacting the stromal microenvironment. Cancer Cell 16(1):55–66. PubMed PMID: 19573812. Pubmed Central PMCID: 2705757

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fukusumi T, Califano JA (2018) The NOTCH pathway in head and neck squamous cell carcinoma. J Dent Res 97(6):645–653. PubMed PMID: 29489439. Pubmed Central PMCID: 5960881

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fukusumi T, Guo TW, Sakai A, Ando M, Ren S, Haft S et al (2018) The NOTCH4-HEY1 pathway induces epithelial-mesenchymal transition in head and neck squamous cell carcinoma. Clin Cancer Res 24(3):619–633. PubMed PMID: 29146722. Pubmed Central PMCID: 6171749

    Article  CAS  PubMed  Google Scholar 

  • Gao YB, Chen ZL, Li JG, Hu XD, Shi XJ, Sun ZM et al (2014) Genetic landscape of esophageal squamous cell carcinoma. Nat Genet. PubMed PMID: 25151357. Epub 2014/08/26. Eng

    Google Scholar 

  • Greenblatt DY, Vaccaro AM, Jaskula-Sztul R, Ning L, Haymart M, Kunnimalaiyaan M et al (2007) Valproic acid activates notch-1 signaling and regulates the neuroendocrine phenotype in carcinoid cancer cells. Oncologist 12(8):942–951. PubMed PMID: 17766653. Epub 2007/09/04. eng

    Article  CAS  PubMed  Google Scholar 

  • Hatch E, Morrow D, Liu W, Cahill PA, Redmond EM (2015) Ethanol inhibits gamma-secretase proteolytic activity in vascular smooth muscle cells. Alcohol Clin Exp Res 39(11):2115–2122. PubMed PMID: 26443551. Pubmed Central PMCID: 4624494. Epub 2015/10/08. eng

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kagawa S, Natsuizaka M, Whelan KA, Facompre N, Naganuma S, Ohashi S et al (2015) Cellular senescence checkpoint function determines differential Notch1-dependent oncogenic and tumor-suppressor activities. Oncogene 34(18):2347–2359. PubMed PMID: 24931169. Pubmed Central PMCID: 4268095

    Article  CAS  PubMed  Google Scholar 

  • Kang X, Chen K, Li Y, Li J, D’Amico TA, Chen X (2015) Personalized targeted therapy for esophageal squamous cell carcinoma. World J Gastroenterol 21(25):7648–7658. PubMed PMID: 26167067. Pubmed Central PMCID: 4491954

    Article  PubMed  PubMed Central  Google Scholar 

  • Kasagi Y, Chandramouleeswaran PM, Whelan KA, Tanaka K, Giroux V, Sharma M et al (2018) The esophageal organoid system reveals functional interplay between Notch and cytokines in reactive epithelial changes. Cell Mol Gastroenterol Hepatol 5(3):333–352. PubMed PMID: 29552622. Pubmed Central PMCID: PMC5852293

    Article  PubMed  PubMed Central  Google Scholar 

  • Li K, Li Y, Wu W, Gordon WR, Chang DW, Lu M et al (2008) Modulation of notch signaling by antibodies specific for the extracellular negative regulatory region of NOTCH3. J Biol Chem 283(12):8046–8054. PubMed PMID: 18182388

    Article  CAS  PubMed  Google Scholar 

  • Lin DC, Hao JJ, Nagata Y, Xu L, Shang L, Meng X et al (2014) Genomic and molecular characterization of esophageal squamous cell carcinoma. Nat Genet 46(5):467–473. PubMed PMID: 24686850. Pubmed Central PMCID: 4070589. Epub 2014/04/02. eng

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu T, Zhang X, So CK, Wang S, Wang P, Yan L et al (2007) Regulation of Cdx2 expression by promoter methylation, and effects of Cdx2 transfection on morphology and gene expression of human esophageal epithelial cells. Carcinogenesis 28(2):488–496. PubMed PMID: 16990345. Epub 2006/09/23. eng

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Xiong Z, Beasley A, D’Amico T, Chen XL (2016a) Personalized and targeted therapy of esophageal squamous cell carcinoma: an update. Ann N Y Acad Sci 1381(1):66–73. PubMed PMID: 27399176. Pubmed Central PMCID: 5083215

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu W, Snell JM, Jeck WR, Hoadley KA, Wilkerson MD, Parker JS et al (2016b) Subtyping sub-Saharan esophageal squamous cell carcinoma by comprehensive molecular analysis. JCI Insight 1(16):e88755. PubMed PMID: 27734031. Pubmed Central PMCID: 5053149. Epub 2016/10/14. eng

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu X, Zhang M, Ying S, Zhang C, Lin R, Zheng J et al (2017) Genetic alterations in esophageal tissues from squamous dysplasia to carcinoma. Gastroenterology 153(1):166–177. PubMed PMID: 28365443. Epub 2017/04/04. eng

    Article  CAS  PubMed  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. PubMed PMID: 21948802. Pubmed Central PMCID: 3182047. Epub 2011/09/29. eng

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martincorena I, Fowler JC, Wabik A, Lawson ARJ, Abascal F, Hall MWJ et al (2018) Somatic mutant clones colonize the human esophagus with age. Science 362(6417):911–917. PubMed PMID: 30337457. Pubmed Central PMCID: PMC6298579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Menke V, van Es JH, de Lau W, van den Born M, Kuipers EJ, Siersema PD et al (2010) Conversion of metaplastic Barrett’s epithelium into post-mitotic goblet cells by gamma-secretase inhibition. Dis Model Mech 3(1–2):104–110. PubMed PMID: 20075383

    Article  CAS  PubMed  Google Scholar 

  • Meurette O, Mehlen P (2018) Notch signaling in the tumor microenvironment. Cancer Cell 34(4):536–548. PubMed PMID: 30146333

    Article  CAS  PubMed  Google Scholar 

  • Meyers JM, Spangle JM, Munger K (2013) The human papillomavirus type 8 E6 protein interferes with NOTCH activation during keratinocyte differentiation. J Virol 87(8):4762–4767. PubMed PMID: 23365452. Pubmed Central PMCID: 3624394. Epub 2013/02/01. eng

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morrow DJ, Avissar NE, Toia L, Redmond EM, Watson TJ, Jones C et al (2009) Pathogenesis of Barrett’s esophagus: bile acids inhibit the Notch signaling pathway with induction of CDX2 gene expression in human esophageal cells. Surgery 146(4):714–721. discussion 21–2. PubMed PMID: 19789031. Pubmed Central PMCID: PMC3371765

    Article  PubMed  Google Scholar 

  • Morrow D, Cullen JP, Liu W, Cahill PA, Redmond EM (2010) Alcohol inhibits smooth muscle cell proliferation via regulation of the Notch signaling pathway. Arterioscler Thromb Vasc Biol 30(12):2597–2603. PubMed PMID: 20930168. Pubmed Central PMCID: 3371770. Epub 2010/10/12. eng

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nandagopal N, Santat LA, LeBon L, Sprinzak D, Bronner ME, Elowitz MB (2018) Dynamic ligand discrimination in the Notch signaling pathway. Cell 172(4):869–80.e19. PubMed PMID: 29398116. Pubmed Central PMCID: 6414217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Natsuizaka M, Whelan KA, Kagawa S, Tanaka K, Giroux V, Chandramouleeswaran PM et al (2017) Interplay between Notch1 and Notch3 promotes EMT and tumor initiation in squamous cell carcinoma. Nat Commun 8(1):1758. PubMed PMID: 29170450. Pubmed Central PMCID: 5700926

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nowell CS, Radtke F (2017) Notch as a tumour suppressor. Nat Rev Cancer 17(3):145–159. PubMed PMID: 28154375

    Article  CAS  PubMed  Google Scholar 

  • Nyman PE, Buehler D, Lambert PF (2018) Loss of function of canonical notch signaling drives head and neck carcinogenesis. Clin Cancer Res 24(24):6308–6318. PubMed PMID: 30087145. Pubmed Central PMCID: 6295262

    Article  PubMed  PubMed Central  Google Scholar 

  • Ohashi S, Natsuizaka M, Yashiro-Ohtani Y, Kalman RA, Nakagawa M, Wu L et al (2010) NOTCH1 and NOTCH3 coordinate esophageal squamous differentiation through a CSL-dependent transcriptional network. Gastroenterology 139(6):2113–2123. PubMed PMID: 20801121. Pubmed Central PMCID: 2997138. Epub 2010/08/31. eng

    Article  CAS  PubMed  Google Scholar 

  • Ohashi S, Natsuizaka M, Naganuma S, Kagawa S, Kimura S, Itoh H et al (2011) A NOTCH3-mediated squamous cell differentiation program limits expansion of EMT-competent cells that express the ZEB transcription factors. Cancer Res 71(21):6836–6847. PubMed PMID: 21890822. Pubmed Central PMCID: 3206139. Epub 2011/09/06. eng

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Okuyama R, Tagami H, Aiba S (2008) Notch signaling: its role in epidermal homeostasis and in the pathogenesis of skin diseases. J Dermatol Sci 49(3):187–194. PubMed PMID: 17624739. Epub 2007/07/13. eng

    Article  PubMed  CAS  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):S497–S504. PubMed PMID: 24419754. Pubmed Central PMCID: 4097979. Epub 2014/01/15. eng

    Article  PubMed  Google Scholar 

  • Pinchot SN, Jaskula-Sztul R, Ning L, Peters NR, Cook MR, Kunnimalaiyaan M et al (2011) Identification and validation of Notch pathway activating compounds through a novel high-throughput screening method. Cancer 117(7):1386–1398. PubMed PMID: 21425138. Pubmed Central PMCID: 3117093. Epub 2011/03/23. eng

    Article  CAS  PubMed  Google Scholar 

  • Qin HD, Liao XY, Chen YB, Huang SY, Xue WQ, Li FF et al (2016) Genomic characterization of esophageal squamous cell carcinoma reveals critical genes underlying tumorigenesis and poor prognosis. Am J Hum Genet 98(4):709–727. PubMed PMID: 27058444. Pubmed Central PMCID: 4833434. Epub 2016/04/09. eng

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ranganathan P, Weaver KL, Capobianco AJ (2011) Notch signalling in solid tumours: a little bit of everything but not all the time. Nat Rev Cancer 11(5):338–351. PubMed PMID: 21508972. Epub 2011/04/22. eng

    Article  CAS  PubMed  Google Scholar 

  • Restivo G, Nguyen BC, Dziunycz P, Ristorcelli E, Ryan RJ, Ozuysal OY et al (2011) IRF6 is a mediator of Notch pro-differentiation and tumour suppressive function in keratinocytes. EMBO J 30(22):4571–4585. PubMed PMID: 21909072. Pubmed Central PMCID: 3243593. Epub 2011/09/13. eng

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sander GR, Powell BC (2004) Expression of notch receptors and ligands in the adult gut. J Histochem Cytochem 52(4):509–516. PubMed PMID: 15034002

    Article  CAS  PubMed  Google Scholar 

  • Sawada G, Niida A, Uchi R, Hirata H, Shimamura T, Suzuki Y et al (2016) Genomic landscape of esophageal squamous cell carcinoma in a Japanese population. Gastroenterology 150(5):1171–1182. PubMed PMID: 26873401. Epub 2016/02/14. eng

    Article  PubMed  Google Scholar 

  • Sawangarun W, Mandasari M, Aida J, Morita KI, Kayamori K, Ikeda T et al (2018) Loss of Notch1 predisposes oro-esophageal epithelium to tumorigenesis. Exp Cell Res 372(2):129–140. PubMed PMID: 30266659

    Article  CAS  PubMed  Google Scholar 

  • Schneider KJ, Scheer M, Suhr M, Clemens DL (2012) Ethanol administration impairs pancreatic repair after injury. Pancreas 41(8):1272–1279. PubMed PMID: 22617711. Pubmed Central PMCID: 3479327. Epub 2012/05/24. eng

    Article  CAS  PubMed  Google Scholar 

  • Shibata T, Kokubu A, Saito S, Narisawa-Saito M, Sasaki H, Aoyagi K et al (2011) NRF2 mutation confers malignant potential and resistance to chemoradiation therapy in advanced esophageal squamous cancer. Neoplasia 13(9):864–873. PubMed PMID: 21969819. Pubmed Central PMCID: PMC3182278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67(1):7–30. PubMed PMID: 28055103. Epub 2017/01/06. eng

    Article  PubMed  Google Scholar 

  • Song Y, Li L, Ou Y, Gao Z, Li E, Li X et al (2014) Identification of genomic alterations in oesophageal squamous cell cancer. Nature 509(7498):91–95. PubMed PMID: 24670651

    Article  CAS  PubMed  Google Scholar 

  • Song B, Cui H, Li Y, Cheng C, Yang B, Wang F et al (2016) Mutually exclusive mutations in NOTCH1 and PIK3CA associated with clinical prognosis and chemotherapy responses of esophageal squamous cell carcinoma in China. Oncotarget 7(3):3599–3613. PubMed PMID: 26528858. Pubmed Central PMCID: 4823130

    Article  PubMed  Google Scholar 

  • Steinbuck MP, Winandy S (2018) A review of Notch processing with new insights into ligand-independent notch signaling in T-cells. Front Immunol 9:1230. PubMed PMID: 29910816. Pubmed Central PMCID: 5992298

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sun W, Gaykalova DA, Ochs MF, Mambo E, Arnaoutakis D, Liu Y et al (2014) Activation of the NOTCH pathway in head and neck cancer. Cancer Res 74(4):1091–1104. PubMed PMID: 24351288. Pubmed Central PMCID: 3944644

    Article  CAS  PubMed  Google Scholar 

  • Tadeu AM, Horsley V (2013) Notch signaling represses p63 expression in the developing surface ectoderm. Development 140(18):3777–3786. PubMed PMID: 23924630. Pubmed Central PMCID: 3754476. Epub 2013/08/09. eng

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tomasetti C, Li L, Vogelstein B (2017a) Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention. Science 355(6331):1330–1334. PubMed PMID: 28336671. Pubmed Central PMCID: PMC5852673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tomasetti C, Durrett R, Kimmel M, Lambert A, Parmigiani G, Zauber A et al (2017b) Role of stem-cell divisions in cancer risk. Nature 548(7666):E13–EE4. PubMed PMID: 28796214

    Article  CAS  PubMed  Google Scholar 

  • Tomasetti C, Poling J, Roberts NJ, London NR Jr, Pittman ME, Haffner MC et al (2019) Cell division rates decrease with age, providing a potential explanation for the age-dependent deceleration in cancer incidence. Proc Natl Acad Sci U S A 116(41):20482–20488. PubMed PMID: 31548407. Pubmed Central PMCID: PMC6789572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wakabayashi N, Shin S, Slocum SL, Agoston ES, Wakabayashi J, Kwak MK et al (2010) Regulation of notch1 signaling by nrf2: implications for tissue regeneration. Sci Signal 3(130):ra52. PubMed PMID: 20628156. Pubmed Central PMCID: 2932745. Epub 2010/07/16. eng

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wakabayashi N, Skoko JJ, Chartoumpekis DV, Kimura S, Slocum SL, Noda K et al (2013) Notch-nrf2 axis: regulation of nrf2 gene expression and cytoprotection by notch signaling. Mol Cell Biol 34(4):653–663. PubMed PMID: 24298019. Epub 2013/12/04. eng

    Article  PubMed  CAS  Google Scholar 

  • Wang X, Pasolli HA, Williams T, Fuchs E (2008) AP-2 factors act in concert with Notch to orchestrate terminal differentiation in skin epidermis. J Cell Biol 183(1):37–48. PubMed PMID: 18824566. Pubmed Central PMCID: 2557040. Epub 2008/10/01. eng

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang YC, Wang ZQ, Yuan Y, Ren T, Ni PZ, Chen LQ (2018) Notch signaling pathway is inhibited in the development of Barrett’s esophagus: an in vivo and in vitro study. Can J Gastroenterol Hepatol 2018:4149317. PubMed PMID: 29785394. Pubmed Central PMCID: 5892280

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu S, Powers S, Zhu W, Hannun YA (2016) Substantial contribution of extrinsic risk factors to cancer development. Nature 529(7584):43–47. PubMed PMID: 26675728. Pubmed Central PMCID: PMC4836858

    Article  CAS  PubMed  Google Scholar 

  • Wyche TP, Dammalapati A, Cho H, Harrison AD, Kwon GS, Chen H et al (2014) Thiocoraline activates the notch pathway in carcinoids and reduces tumor progression in vivo. Cancer Gene Ther 21(12):518–525. PubMed PMID: 25412645. Pubmed Central PMCID: 4270822. Epub 2014/11/22. eng

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiong Z, Ren S, Chen H, Liu Y, Huang C, Zhang YL et al (2018) PAX9 regulates squamous cell differentiation and carcinogenesis in the oro-oesophageal epithelium. J Pathol 244(2):164–175. PubMed PMID: 29055049. Pubmed Central PMCID: PMC5842438

    Article  CAS  PubMed  Google Scholar 

  • Ye Q, Jiang J, Zhan G, Yan W, Huang L, Hu Y et al (2016) Small molecule activation of NOTCH signaling inhibits acute myeloid leukemia. Sci Rep 6:26510. PubMed PMID: 27211848. Pubmed Central PMCID: 4876435. Epub 2016/05/24. eng

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yizhak K, Aguet F, Kim J, Hess JM, Kubler K, Grimsby J et al (2019) RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues. Science 364(6444) PubMed PMID: 31171663

    Google Scholar 

  • Yokoyama A, Kakiuchi N, Yoshizato T, Nannya Y, Suzuki H, Takeuchi Y et al (2019) Age-related remodelling of oesophageal epithelia by mutated cancer drivers. Nature 565(7739):312–317. PubMed PMID: 30602793

    Article  CAS  PubMed  Google Scholar 

  • Yu XM, Phan T, Patel PN, Jaskula-Sztul R, Chen H (2013) Chrysin activates Notch1 signaling and suppresses tumor growth of anaplastic thyroid carcinoma in vitro and in vivo. Cancer 119(4):774–781. PubMed PMID: 22991264. Pubmed Central PMCID: 3528831. Epub 2012/09/20. eng

    Article  CAS  PubMed  Google Scholar 

  • Yuan Y, Tong TJ, Zeng XX, Yang YS, Wang ZQ, Wang YC et al (2017) Longitudinal study of esophageal mucosal damage after esophagectomy and gastric interposition: relationship between reflux-related mucosal injury and Notch signaling. J Thorac Dis 9(12):5249–5260. PubMed PMID: 29312733. Pubmed Central PMCID: 5757047

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang L, Zhou Y, Cheng C, Cui H, Cheng L, Kong P et al (2015) Genomic analyses reveal mutational signatures and frequently altered genes in esophageal squamous cell carcinoma. Am J Hum Genet 96(4):597–611. PubMed PMID: 25839328. Pubmed Central PMCID: 4385186. Epub 2015/04/04. eng

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Yang Y, Jiang M, Huang SX, Zhang W, Al Alam D et al (2018) 3D modeling of esophageal development using human PSC-derived basal progenitors reveals a critical role for Notch signaling. Cell Stem Cell 23(4):516–29.e5. PubMed PMID: 30244870. Pubmed Central PMCID: 6282026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhong R, Bao R, Faber PW, Bindokas VP, Bechill J, Lingen MW et al (2015) Notch1 activation or loss promotes HPV-induced oral tumorigenesis. Cancer Res 75(18):3958–3969. PubMed PMID: 26294213. Pubmed Central PMCID: 4573897

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Thoracic Surgery, National Cancer Center, Cancer Hospital of Chinese Academy of Medical Sciences, Beijing, China

    Yong Li

  2. Cancer Research Program, Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, NC, USA

    Yong Li, Yahui Li & Xiaoxin Chen

  3. Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Xiaoxin Chen

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  1. Yong Li
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  2. Yahui Li
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Correspondence to Xiaoxin Chen .

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Editors and Affiliations

  1. Department of Dermatology, Saarland University Medical Center, Homburg, Saarland, Germany

    Jörg Reichrath

  2. Department of Dermatology, Saarland University Medical Center, Homburg, Saarland, Germany

    Sandra Reichrath

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Li, Y., Li, Y., Chen, X. (2021). NOTCH and Esophageal Squamous Cell Carcinoma. 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_5

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