Human Schlafen 5 Inhibits Proliferation and Promotes Apoptosis in Lung Adenocarcinoma via the PTEN/PI3K/AKT/mTOR Pathway.
Human Schlafen 5 Inhibits Proliferation and Promotes Apoptosis in Lung Adenocarcinoma via the PTEN/PI3K/AKT/mTOR Pathway.
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DOI：
10.1155/2021/6628682
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发表时间：
2021
影响因子：
--
通讯作者：
Lu C
中科院分区：
文献类型：
--
作者：
Gu X;Zhou L;Chen L;Pan H;Zhao R;Guang W;Wan G;Zhang P;Liu D;Deng LL;Zhao W;Lu C
据我们的实验室和其他研究人员报道，人类Schlafen 5 （SLFN5）可以抑制或促进几种特定类型癌细胞的增殖。我们很好奇它在肺腺癌（LUAC）中的意义，这是一种高发病率和高死亡率的恶性肿瘤。用慢病毒稳定转染SLFN5特异性shRNA进行敲低和SLFN5全长编码序列进行过表达，在LUAC细胞中进行体外和体内裸鼠增殖分析。收集临床LUAC样本进行SLFN5蛋白水平的免疫组化分析。我们发现，内源性SLFN5的下调上调了癌细胞的增殖，抑制了细胞凋亡。此外，在裸鼠异种移植瘤模型中也观察到SLFN5对增殖的抑制作用。而过表达外源SLFN5则在体外和体内抑制细胞增殖，促进细胞凋亡。在信号通路上，我们发现SLFN5正调控10号染色体上的磷酸酶和紧张素同源物（PTEN），而其下游信号通路AKT/哺乳动物雷帕霉素靶蛋白（mTOR）则受到抑制。此外，与邻近正常组织相比，肺腺癌组织中SLFN5蛋白水平明显降低。综上所述，这些提示人类SLFN5通过PTEN/PI3K/AKT/mTOR通路抑制LUAC的进展，为未来开发肺癌治疗药物提供了潜在靶点。
Human Schlafen 5 (SLFN5) is reported to inhibit or promote the proliferation of several specific types of cancer cells by our lab and other researchers. We are curious about its implications in lung adenocarcinoma (LUAC), a malignant tumor with a high incidence rate and high mortality. Lentiviral stable transfections of SLFN5-specific shRNA for knockdown and SLFN5 full-length coding sequence for overexpression were performed in LUAC cell for proliferation analysis in vitro and in vivo in nude mice. Clinical LUAC samples were collected for immunohistochemical analysis of SLFN5 protein levels. We found that knockdown of endogenous SLFN5 upregulates cancer cell proliferation while inhibiting apoptosis. Besides, SLFN5 inhibition on proliferation was also observed in a nude mouse xenograft model. In contrast, overexpression of exogenous SLFN5 inhibited cell proliferation in vitro and in vivo and promoted apoptosis. As to the signaling pathway, we found phosphatase and tensin homolog on chromosome 10 (PTEN) was positively regulated by SLFN5, while its downstream signaling pathway AKT/mammalian target of rapamycin (mTOR) was inhibited. Moreover, compared with adjacent normal tissues, SLFN5 protein levels were markedly decreased in lung adenocarcinoma tissues. In conclusion, these suggest that human SLFN5 plays inhibitory roles in LUAC progression through the PTEN/PI3K/AKT/mTOR pathway, providing a potential target for developing drugs for lung cancer therapy in the future.
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影响因子：
3.3
作者：
Marsit, CJ;Zheng, SC;Kelsey, KT
通讯作者：
Kelsey, KT
DOI：
10.1016/j.bbrc.2008.03.032
发表时间：
2008-05-23
影响因子：
3.1
作者：
Neumann, Brent;Zhao, Liang;Gonda, Thomas J.
通讯作者：
Gonda, Thomas J.
影响因子：
9.2
作者：
Patel, L;Pass, I;Macphee, CH
通讯作者：
Macphee, CH
DOI：
10.1073/pnas.95.9.4997
发表时间：
1998-04-28
影响因子：
11.1
作者：
Jürgensmeier, JM;Xie, ZH;Reed, JC
通讯作者：
Reed, JC
影响因子：
4.4
作者：
Geserick, P;Kaiser, F;Zerrahn, J
通讯作者：
Zerrahn, J