|Table of Contents|

FAT1 inhibits the proliferation of esophageal squamous cell carcinoma by regulating Hippo signaling pathway

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 05
Page:
794-799
Research Field:
Publishing date:

Info

Title:
FAT1 inhibits the proliferation of esophageal squamous cell carcinoma by regulating Hippo signaling pathway
Author(s):
ZHANG Fanyu1; 2; 3; SHAN Chengyuan1; 2; 3; ZHAI Yuanfang2; 3; ZOU Siwei1; 2; 3; LI Guodong4; HU Xiaoling1; 2; 3
1.Department of Pharmacology;2.Key Laboratory of Cellular Physiology of the Ministry of Education;3.Translational Medicine Research Center,Shanxi Medicial University,Shanxi Taiyuan 030001,China;4.Department of Otolaryngology,the Fifth Clinical Medical College of Shanxi Medical University,Shanxi Taiyuan 030012,China.
Keywords:
esophageal squamous cell carcinoma; FAT1; Hippo signaling pathway; proliferation
PACS:
R735.1
DOI:
10.3969/j.issn.1672-4992.2023.05.002
Abstract:
Objective：To investigate the effect and possible molecular mechanism of FAT atypical cadherin 1 (FAT1) on cell proliferation of esophageal squamous cell carcinoma (ESCC).Methods:FAT1 mutation and survival analysis were performed by using TCGA databases.Lentivirus were used to construct cell lines for stable FAT1 knockdown.The effect of FAT1 on cell proliferation was detected by MTT and colony formation assay in KYSE450 and TE9 cell lines.The expressions of Hippo signaling pathway related markers were detected by Western Blot.And expression of Yes1 associated transcriptional regulator (YAP) at animal tissue level was detected by immunohistochemistry.Results:The analysis of TCGA database showed that FAT1 was mutated across 31 cancer types.ESCC patients with high FAT1 expression had a better prognosis.FAT1 knockdown promoted the proliferation of ESCC cells and changed the protein level of Hippo signaling pathway related genes.And immunohistochemistry results showed that FAT1 knockdown enhanced the expression of YAP in the nucleus.Conclusion:FAT1 inhibits ESCC cell proliferation by regulating Hippo signaling pathway.

References:

［1］BRAY F,FERLAY J,SOERJOMATARAM I,et al.Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］.CA Cancer J Clin,2018,68(6):394-424.
［2］ABNET CC,ARNOLD M,WEI WQ.Epidemiology of esophageal squamous cell carcinoma［J］.Gastroenterology,2018,154(2):360-373.
［3］ZENG H,ZHENG R,ZHANG S,et al.Esophageal cancer statistics in China,2011:Estimates based on 177 cancer registries［J］.Thorac Cancer,2016,7(2):232-237.
［4］KATOH M.Function and cancer genomics of FAT family genes (review)［J］.Int J Oncol,2012,41(6):1913-1918.
［5］TANOUE T,TAKEICHI M.New insights into Fat cadherins［J］.J Cell Sci,2005,118(Pt 11):2347-2353.
［6］MORRIS LG,KAUFMAN AM,GONG Y,et al.Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation［J］.Nat Genet,2013,45(3):253-261.
［7］SADEQZADEH E,DE BOCK CE,ZHANG XD,et al.Dual processing of FAT1 cadherin protein by human melanoma cells generates distinct protein products［J］.J Biol Chem,2011,286(32):28181-28191.
［8］VALLETTA D,CZECH B,SPRUSS T,et al.Regulation and function of the atypical cadherin FAT1 in hepatocellular carcinoma［J］.Carcinogenesis,2014,35(6):1407-1415.
［9］KIM KT,KIM BS,KIM JH.Association between FAT1 mutation and overall survival in patients with human papillomavirus-negative head and neck squamous cell carcinoma［J］.Head Neck,2016,38 Suppl 1:E2021.
［10］CUI Y,CHEN H,XI R,et al.Whole-genome sequencing of 508 patients identifies key molecular features associated with poor prognosis in esophageal squamous cell carcinoma［J］.Cell Res,2020,30(10):902-913.
［11］HU X,ZHAI Y,KONG P,et al.FAT1 prevents epithelial mesenchymal transition (EMT) via MAPK/ERK signaling pathway in esophageal squamous cell cancer［J］.Cancer Lett,2017,397:83-93.
［12］LI Z,RAZAVI P,LI Q,et al.Loss of the FAT1 tumor suppressor promotes resistance to CDK4/6 inhibitors via the Hippo pathway［J］.Cancer Cell,2018,34(6):893-905 e8.
［13］JIANG S,ZHU Y,CHEN Z,et al.S100A14 inhibits cell growth and epithelial-mesenchymal transition (EMT) in prostate cancer through FAT1-mediated Hippo signaling pathway［J］.Hum Cell,2021,34(4):1215-1226.
［14］MARTIN D,DEGESE MS,VITALE-CROSS L,et al.Assembly and activation of the Hippo signalome by FAT1 tumor suppressor［J］.Nat Commun,2018,9(1):2372.
［15］PICCOLO S,DUPONT S,CORDENONSI M.The biology of YAP/TAZ:Hippo signaling and beyond［J］.Physiol Rev,2014,94(4):1287-1312.
［16］MISRA JR,IRVINE KD.The Hippo signaling network and its biological functions［J］.Annu Rev Genet,2018,52(1):65-87.
［17］XU C,WANG L,ZHANG Y,et al.Tubule-specific MST1/2 deficiency induces CKD via YAP and non-YAP mechanisms［J］.J Am Soc Nephrol,2020,31(5):946-961.
［18］ANDO T,ARANG N,WANG Z,et al.EGFR regulates the Hippo pathway by promoting the tyrosine phosphorylation of MOB1［J］.Commun Biol,2021,4(1):1237.
［19］WANG D,HE J,DONG J,et al.The Hippo pathway in gynecological malignancies［J］.Am J Cancer Res,2020,10(2):610-629.
［20］ALDERTON GK,BORDON Y.Tumour immunotherapy-leukocytes take up the fight［J］.Nat Rev Immunol,2012,12(4):237.
［21］LI M,ZHONG Y,WANG M.Fat1 suppresses the tumor-initiating ability of nonsmall cell lung cancer cells by promoting Yes-associated protein 1 nuclear-cytoplasmic translocation［J］.Environ Toxicol,2021,36(11):2333-2341.
［22］SRIVASTAVA C,IRSHAD K,DIKSHIT B,et al.FAT1 modulates EMT and stemness genes expression in hypoxic glioblastoma［J］.Int J Cancer,2018,142(4):805-812.
［23］LIU H,DU S,LEI T,et al.Multifaceted regulation and functions of YAP/TAZ in tumors (review)［J］.Oncol Rep,2018,40(1):16-28.
［24］MA S,MENG Z,CHEN R,et al.The Hippo pathway:Biology and pathophysiology［J］.Annu Rev Biochem,2019,88:577-604.
［25］DEY A,VARELAS X,GUAN KL.Targeting the Hippo pathway in cancer,fibrosis,wound healing and regenerative medicine［J］.Nat Rev Drug Discov,2020,19(7):480-494.
［26］HUANG C,YUAN W,LAI C,et al.EphA2-to-YAP pathway drives gastric cancer growth and therapy resistance［J］.Int J Cancer,2020,146(7):1937-1949.
［27］WANG Y,XU X,MAGLIC D,et al.Comprehensive molecular characterization of the Hippo signaling pathway in cancer［J］.Cell Rep,2018,25(5):1304-1317 e5.

Memo

Memo:
山西省自然科学研究面上项目（编号：202203021211226，202103021224368）；National Natural Science Foundation of China（No.81802825）;国家自然科学基金项目（编号：81802825）
Last Update: 2023-01-31