Abstract: 【Abstract】〓Objective〓To study the effect of shGLUD1 on CRC cell migration and invasion, and elucidate the underline mechanisms. Methods〓The effect of GLUD1 knock-down was confirmed by Western blot analysis and qRT-PCR. The functional role of shGLUD1 on CRC cell motility was evaluated by transwell invasion assay and wound healing assay. Western blot and qRT-PCR were used to determine the expression of EMT markers and STAT3 phosphorylation. Results〓shGLUD1 mediated by lentivirus could availably down-regulate GLUD1 expression both at protein and mRNA levels. GLUD1 knock-down could significant suppress CRC cell invasion and migration in vitro, and decrease STAT3 phosphorylation and EMT. Additionally, STAT3 pathway blockage could significant attenuate the migration and invasion ability of CRC cells, and suppress EMT. Conclusion〓These results indicate that GLUD1 plays a critical role in CRC progression via STAT3 mediated EMT induction.

Key words: EMT, GLUD1, Colorectal cancer

摘要： 【摘要】 目的 观察GLUD1对结直肠癌细胞侵袭和迁移能力的影响,探讨其可能的分子机制。方法〓采用慢病毒转染下调GLUD1的表达,Transwell侵袭实验检测shGLUD1对肠癌细胞Lovo和SW480侵袭能力的影响,划痕实验检测shGLUD1对Lovo和SW480迁移能力的影响,Western blot检测GLUD1和AG490对E-cadherin、Vimentin、ZEB1、STAT3及pSTAT3表达的影响。结果〓慢病毒转染shGLUD1可显著下调GLUD1在结肠癌细胞中的表达;下调GLUD1的表达可抑制结肠癌细胞Lovo和SW480的侵袭迁移能力;GLUD1可促进STAT3磷酸化,以及上调Vimentin、ZEB1和下调E-cadherin的表达;而AG490处理则可抑制STAT3的磷酸化,上调E-cadherin和下调Vimentin、ZEB1的表达。结论〓GLUD1可通过活化STAT3信号调控上皮间质转化(EMT),进而促进结肠癌细胞的侵袭迁移能力。

关键词: 上皮间质转化, 谷氨酸脱氢酶, 结直肠癌