Chen Hui, Wang Dongliang, Liu Yuling
Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China.
Mol Med Rep. 2016 Apr;13(4):3613-8. doi: 10.3892/mmr.2016.4946. Epub 2016 Feb 29.
SAM and SH3 domain containing 1 (SASH1), a member of the SLY-family of signal adapter proteins, is a candidate tumor suppressor in several types of cancer. However, the role of SASH1 in cervical cancer remains to be elucidated. Therefore, in the present study, the role of SASH1 in cervical cancer and the underlying mechanism was investigated. Cell proliferation was detected by the MTT assay. Cell invasion was measured by Transwell assay. The mRNA expression levels of SASH1, matrix metalloproteinase (MMP)‑2 and MMP‑9 were determined by reverse transcription quantitative polymerase chain reaction. The protein expression levels of SASH1, MMP‑2, MMP‑9 and focal adhesion kinase (FAK) were determined by western blot analysis. The results demonstrated that SASH1 was downregulated in cervical cancer tissues and cell lines. Subsequently, a vector that overexpresses SASH1 was constructed. Overexpression of SASH1 was found to significantly inhibit cervical cancer cell proliferation and invasion, and also significantly reduce the expression of MMP‑2 and MMP‑9 in cancer cells. In addition, SASH1 modulated the FAK signaling pathway. Overexpression of SASH1 suppressed the expression of FAK in cancer cells. Taken together, the results suggested that SASH1 inhibits cervical cancer cell proliferation and invasion by suppressing the FAK pathway.
含SAM和SH3结构域蛋白1(SASH1)是信号衔接蛋白SLY家族的成员,是几种癌症类型中的候选肿瘤抑制因子。然而,SASH1在宫颈癌中的作用仍有待阐明。因此,在本研究中,对SASH1在宫颈癌中的作用及其潜在机制进行了研究。通过MTT法检测细胞增殖。通过Transwell法检测细胞侵袭。通过逆转录定量聚合酶链反应测定SASH1、基质金属蛋白酶(MMP)-2和MMP-9的mRNA表达水平。通过蛋白质印迹分析测定SASH1、MMP-2、MMP-9和粘着斑激酶(FAK)的蛋白表达水平。结果表明,SASH1在宫颈癌组织和细胞系中表达下调。随后,构建了过表达SASH1的载体。发现SASH1过表达可显著抑制宫颈癌细胞的增殖和侵袭,还可显著降低癌细胞中MMP-2和MMP-9的表达。此外,SASH1调节FAK信号通路。SASH1过表达抑制癌细胞中FAK的表达。综上所述,结果表明SASH1通过抑制FAK通路抑制宫颈癌细胞的增殖和侵袭。