Polycystin-1 affects cancer cell behaviour and interacts with mTOR and Jak signalling pathways in cancer cell lines
Polycystin-1 affects cancer cell behaviour and interacts with mTOR and Jak signalling pathways in cancer cell lines
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DOI：
10.1111/jcmm.14506
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发表时间：
2019-06-28
影响因子：
5.3
通讯作者：
Koutsilieris, Michael
中科院分区：
文献类型：
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作者：
Papavassiliou, Kostas A.;Zoi, Ilianna;Koutsilieris, Michael
多囊肾病(PKD)是由编码多囊蛋白-1(PC1)和多囊蛋白-2(PC2)的PKD1和PKD2基因突变引起的，与癌症有共同的细胞缺陷，如细胞增殖失控、分化异常和细胞凋亡增加。有趣的是，PC1调节许多信号通路，包括Jak/STAT、mTOR、Wnt、AP-1和Calcineurin-NFAT，这些信号通路也被癌细胞用来发送信号，使它们能够获得和维持恶性表型。然而，多囊蛋白与癌症之间的分子关系尚不清楚。在这项研究中，我们使用胶质母细胞瘤(GOS3)、前列腺(PC3)、乳腺(MCF7)、肺癌(A549)和结直肠癌(HT29)癌细胞株来研究PC1在癌症生物学中的作用。我们的体外实验结果表明，PC1促进GOS3细胞的迁移，抑制A549细胞的迁移。此外，PC1促进GOS3细胞的增殖，而抑制MCF7、A549和HT29细胞的增殖。我们还发现，PC1在GOS3细胞中上调mTOR信号转导，下调JAK信号转导，而在PC3和HT29细胞中上调mTOR信号转导。总之，我们的研究表明，PC1调节细胞的增殖和迁移，并在不同的癌细胞系中与mTOR和JAK信号通路相互作用。了解多囊藻毒素与癌症相关的分子细节可能有助于确定这种毁灭性疾病的新参与者。
Polycystic Kidney Disease (PKD), which is attributable to mutations in the PKD1 and PKD2 genes encoding polycystin-1 (PC1) and polycystin-2 (PC2) respectively, shares common cellular defects with cancer, such as uncontrolled cell proliferation, abnormal differentiation and increased apoptosis. Interestingly, PC1 regulates many signalling pathways including Jak/STAT, mTOR, Wnt, AP-1 and calcineurin-NFAT which are also used by cancer cells for sending signals that will allow them to acquire and maintain malignant phenotypes. Nevertheless, the molecular relationship between polycystins and cancer is unknown. In this study, we investigated the role of PC1 in cancer biology using glioblastoma (GOS3), prostate (PC3), breast (MCF7), lung (A549) and colorectal (HT29) cancer cell lines. Our in vitro results propose that PC1 promotes cell migration in GOS3 cells and suppresses cell migration in A549 cells. In addition, PC1 enhances cell proliferation in GOS3 cells but inhibits it in MCF7, A549 and HT29 cells. We also found that PC1 up-regulates mTOR signalling and down-regulates Jak signalling in GOS3 cells, while it up-regulates mTOR signalling in PC3 and HT29 cells. Together, our study suggests that PC1 modulates cell proliferation and migration and interacts with mTOR and Jak signalling pathways in different cancer cell lines. Understanding the molecular details of how polycystins are associated with cancer may lead to the identification of new players in this devastating disease.