title: The Characteristic of S100A7 Induction by the Hippo-YAP Pathway in Cervical and Glossopharyngeal Squamous Cell Carcinoma.
abstract: S100A7 is expressed in many squamous cell carcinomas (SCCs). Our previous study revealed that S100A7 was dramatically induced in several SCC cells and activation of the Hippo pathway significantly promoted S100A7 in epidermoid carcinoma cells. However, whether the Hippo pathway regulates S100A7 expression in SCCs remains largely unknown. Here, we uncover that S100A7 induction by the Hippo-YAP pathway displays different characteristic in cervical and glossopharyngeal SCC. In well differentiated HCC94 cervical cells and FaDu pharyngeal cells, S100A7 is easily induced by both suspension and dense culture, which is accompanied by an increase in YAP phosphorylation and a decrease in nuclear YAP. Strikingly, these correlations of S100A7 and YAP reverse after recovery of cell attachment or relief from dense culture. Further examination finds that S100A7 induction is significantly repressed by nuclear YAP, which is validated by activation or inhibition of the Hippo pathway via loss- and/or gain-of- LATS1 and MST1 function. Subsequently, we prove that TEAD1 is required for YAP transcriptional repression of S100A7. However, S100A7 is hardly induced in poorly differentiated SiHa cervical cells and NCI-H226 pulmonary cells even in suspension or activation of the Hippo pathway. More importantly, cervical and lingual SCC tissues array analyses show that S100A7 expression displays the positive correlation with pYAP-S127 and the negative correlation with nuclear YAP in the majority of well differentiated but not in poorly differentiated tissues. Collectively, our findings demonstrate that the different induction of S100A7 toward activation of the Hippo pathway mainly depends on the degree of cell differentiation in cervical and glossopharyngeal SCC.
authors.affiliation: Key laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Kong
authors.affiliation: Key laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.
authors.forename: Yunguang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.
authors.forename: Enze
authors.initials: E
authors.lastname: Hu
authors.affiliation: Key laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Key laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.
authors.forename: Junhao
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences and Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Jinsan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.
authors.forename: Dacheng
authors.initials: D
authors.lastname: He
authors.affiliation: Key laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Xiao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D000090683:Hippo Signaling Pathway; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D010610:Pharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D040081:Protein Array Analysis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor; C092745:LATS1 protein, human; D017346:Protein Serine-Threonine Kinases