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人类癌基因 SCL/TAL1 中断基因座(STIL)通过 MAPK/ERK、PI3K/Akt 和 AMPK 通路促进前列腺癌的肿瘤生长。

The human oncogene SCL/TAL1 interrupting locus (STIL) promotes tumor growth through MAPK/ERK, PI3K/Akt and AMPK pathways in prostate cancer.

机构信息

Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Gene. 2019 Feb 20;686:220-227. doi: 10.1016/j.gene.2018.11.048. Epub 2018 Nov 16.

DOI:10.1016/j.gene.2018.11.048
PMID:30453068
Abstract

The morbidity and mortality of prostate cancer (PCa) in China have increased obviously, which became the second leading cause of death in men with cancer. Hedgehog (Hh) signaling pathway is a key signaling pathway involved in the prostate cancer progression. The human oncogene SCL/TAL1 interrupting locus (STIL) can modulate the Hh signaling pathway, but its function in PCa has not been reported. Here, we showed that STIL was increased in high grade prostate cancer tissue. Knockdown of STIL in prostate cancer cells PC-3 and DU 145 significantly decreased the proliferation of cells and induced cellular apoptosis through casepase3/7 mediated pathway. Moreover, the colony formation ability was also inhibited when knockdown of STIL by lentivirus-mediated shRNA. Furthermore, the cellular signaling antibody array analysis revealed which signaling pathway was affected when silencing STIL. Altogether, we found that STIL could affect MAPK/ERK, PI3K/Akt and AMPK signaling pathways, thus promoting cellular proliferation, colony formation and suppressing cellular apoptosis in prostate cancer.

摘要

中国前列腺癌(PCa)的发病率和死亡率明显上升,已成为男性癌症死亡的第二大原因。Hedgehog(Hh)信号通路是参与前列腺癌进展的关键信号通路。人类癌基因 SCL/TAL1 中断位点(STIL)可以调节 Hh 信号通路,但它在 PCa 中的功能尚未报道。在这里,我们发现 STIL 在高级别前列腺癌组织中增加。在前列腺癌细胞 PC-3 和 DU 145 中敲低 STIL 显著降低了细胞的增殖,并通过 caspase3/7 介导的途径诱导细胞凋亡。此外,当通过慢病毒介导的 shRNA 敲低 STIL 时,集落形成能力也受到抑制。此外,细胞信号抗体阵列分析揭示了沉默 STIL 时受影响的信号通路。总的来说,我们发现 STIL 可以影响 MAPK/ERK、PI3K/Akt 和 AMPK 信号通路,从而促进前列腺癌细胞的增殖、集落形成并抑制细胞凋亡。

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