title: S100A7 acts as a dual regulator in promoting proliferation and suppressing squamous differentiation through GATA-3/caspase-14 pathway in A431 cells.
abstract: S100A7 is expressed in many squamous cell carcinomas (SCCs), such as SCC of the skin, and well-differentiated SCC always displays stronger staining of this protein. A431 cells, an epidermal cancer cell line, were selected as a cell model to investigate the roles and mechanism of S100A7 in SCC of the skin. In this study, we demonstrated that the overexpression of S100A7 in A431 cells significantly promoted cell proliferation in vitro and tumor growth in vivo, whereas it suppressed the expression of GATA-3, caspase-14 and three squamous differentiation markers, keratin-1, TG-1 and involucrin. Conversely, the overexpression of caspase-14 not only significantly decreased cell proliferation and delayed tumor growth but also markedly induced the expression of three squamous differentiation markers, whereas S100A7 and GATA-3 were not influenced. Further evidence showed that silencing GATA-3 greatly inhibited the expression of caspase-14 and three differentiation markers, while the expression of S100A7 was not changed; contrary results were obtained when overexpressing GATA-3. Importantly, restoring the expression of GATA-3 and caspase-14 in A431-S100A7 cells could bypass the ability of S100A7 to increase cell viability and repress squamous differentiation. These data suggested that S100A7 expression in SCC may play an important role in the maintenance of SCC cell dedifferentiation, at least in SCC of the skin.
authors: Key Laboratory of Cell Proliferation and Regulation of Ministry of Education, Beijing Normal University, Beijing, China.
authors: Ting
authors: T
authors: Li
authors: Zhi
authors: Z
authors: Qi
authors: Fei
authors: F
authors: Kong
authors: Yunguang
authors: Y
authors: Li
authors: Rui
authors: R
authors: Wang
authors: Weiqing
authors: W
authors: Zhang
authors: Yu
authors: Y
authors: Shang
authors: Lingyun
authors: L
authors: Huang
authors: Dacheng
authors: D
authors: He
authors: Xueyuan
authors: X
authors: Xiao
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D054337:Cell Dedifferentiation / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; C506446:CASP14 protein, human; D020169:Caspases
keywords: GATA-3; S100A7; caspase-14; differentiation; proliferation