Peking University People's Hospital, Beijing 100044, P.R. China.
Oncol Rep. 2013 Sep;30(3):1157-64. doi: 10.3892/or.2013.2563. Epub 2013 Jun 25.
Recent studies have indicated that telomerase activity promotes cancer invasion and metastasis, but the underlying mechanism remains unclear. Several studies have shown that expression of exogenous human telomerase reverse transcriptase (hTERT) can promote motility and invasiveness among telomerase-negative tumor cells, and inhibition of endogenous telomerase activity can reduce invasiveness in tumor cells. However, whether overexpression of hTERT can further enhance the motility and invasiveness of telomerase‑positive tumor cells has yet to be determined. In the present study, we showed that stable overexpression of hTERT can increase telomerase activity and telomere length, which significantly promotes the invasive and metastatic potential of telomerase‑positive HepG2 cells but does not affect cell proliferation. Further analysis suggested that enhanced invasiveness and metastasis may act through corresponding upregulation of mRNA and protein expression of matrix metalloproteinase 9 (MMP9) and Ras homolog gene family member C (RhoC). Our study indicated that exogenous expression of hTERT may promote invasiveness and metastasis through upregulation of MMP9 and RhoC.
最近的研究表明,端粒酶活性促进癌症的侵袭和转移,但潜在的机制尚不清楚。一些研究表明,外源性人端粒酶逆转录酶(hTERT)的表达可以促进端粒酶阴性肿瘤细胞的迁移和侵袭,而内源性端粒酶活性的抑制可以降低肿瘤细胞的侵袭性。然而,hTERT 的过表达是否可以进一步增强端粒酶阳性肿瘤细胞的迁移和侵袭性尚待确定。在本研究中,我们表明 hTERT 的稳定过表达可以增加端粒酶活性和端粒长度,这显著促进了端粒酶阳性 HepG2 细胞的侵袭和转移潜能,但不影响细胞增殖。进一步的分析表明,增强的侵袭和转移可能通过相应地上调基质金属蛋白酶 9(MMP9)和 Ras 同源基因家族成员 C(RhoC)的 mRNA 和蛋白表达来发挥作用。我们的研究表明,外源性表达 hTERT 可能通过上调 MMP9 和 RhoC 来促进侵袭和转移。