Department of Biochemistry and Molecular Biology, the Key Immunopathology Laboratory of Guangdong Province, Medical College of Shantou University, Shantou 515041, China.
Am J Pathol. 2010 Feb;176(2):939-51. doi: 10.2353/ajpath.2010.090118. Epub 2010 Jan 7.
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.
Fascin 在食管鳞状细胞癌（ESCC）中过表达，并且参与 ESCC 细胞的增殖和侵袭。在这项研究中，我们通过免疫组织化学法回顾性地检测了 Fascin 在 ESCC 样本中的表达，结果表明 Fascin 的过表达与患者生存不良有关。在 ESCC 细胞中，RNAi 介导的 Fascin 敲低显著抑制了细胞的增殖和侵袭能力，而在永生化食管上皮细胞中强制表达 Fascin 则加速了细胞的增殖和侵袭能力。为了探讨潜在的机制，我们进行了 cDNA 微阵列分析，以鉴定通过 RNAi 耗尽 Fascin 的细胞系与相应的对照 ESCC 细胞之间的差异基因表达谱。结果表明，296 个基因在 Fascin 耗尽时差异表达。在本研究中，我们重点关注两个下调基因：CYR61 和 CTGF。我们发现，恢复表达 CYR61 或 CTGF 可恢复 Fascin 表达下调所导致的细胞增殖和侵袭抑制；CYR61 和 CTGF 的蛋白水平在 ESCC 中上调，其表达模式与 Fascin 的过表达相关。最后，信号转导分析表明，Fascin 通过转化生长因子（TGF）-β途径影响 CYR61 和 CTGF 的表达。综上所述，我们提出 Fascin 通过 TGF-β途径调节 CTGF 和 CYR61 的表达来调节 ESCC 细胞的增殖和侵袭。
