Involvement of CYR61 and CTGF in the fascin-mediated proliferation and invasiveness of esophageal squamous cell carcinomas cells.
Fascin is overexpressed in esophageal squamous cell [corrected] carcinoma (ESCC) and involved in the proliferation and invasiveness of ESCC cells. In this study, we retrospectively examined the expression of fascin in ESCC samples by immunohistochemistry and revealed that overexpression of fascin was related to poor patient survival. RNAi-mediated knockdown of fascin in ESCC cells significantly inhibited cell proliferation and invasiveness, whereas forced expression of fascin in immortalized esophageal epithelial cells accelerated cell proliferation and invasiveness. To explore the underlying mechanism, cDNA microarray was performed to identify the differential gene expression profiles between a fascin-depleted cell line by RNAi and the corresponding control ESCC cells. Results showed that 296 genes were differentially expressed on fascin depletion. In this study, we focused on two down-regulated genes: CYR61 and CTGF. We found that restored expression of either CYR61 or CTGF led to a recovery of the suppression of cellular proliferation and invasiveness induced by down-regulation of fascin expression; the protein level of CYR61 and CTGF were up-regulated in ESCCs and their expression pattern correlated with fascin overexpression. Finally, analysis of signal transduction revealed that fascin affected the expressions of CYR61 and CTGF through transforming growth factor (TGF)-beta pathway. Taken together, we propose that fascin regulates the proliferation and invasiveness of ESCC cells by modulating the expression of CTGF and CYR61 via TGF-beta pathway.
Xie
Jian-Jun
JJ
Department of Biochemistry and Molecular Biology, the Key Immunopathology Laboratory of Guangdong Province, Medical College of Shantou University, Shantou 515041, China.
Xu
Li-Yan
LY
Wu
Jian-Yi
JY
Shen
Zhong-Ying
ZY
Zhao
Qing
Q
Du
Ze-Peng
ZP
Lv
Zhuo
Z
Gu
Wei
W
Pan
Feng
F
Xu
Xiu-E
XE
Xie
Dong
D
Li
En-Min
EM
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000502:physiology*; D055515:Cysteine-Rich Protein 61 / Q000235:genetics / Q000502:physiology*; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000502:physiology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D015398:Signal Transduction / Q000235:genetics; D016019:Survival Analysis; D016212:Transforming Growth Factor beta / Q000502:physiology; D014407:Tumor Cells, Cultured
C501848:CCN1 protein, human; C526317:CCN2 protein, human; D002352:Carrier Proteins; D055515:Cysteine-Rich Protein 61; C502658:FSCN1 protein, human; D008840:Microfilament Proteins; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor