Department of Urology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, 710061, China.
Department of Nephrology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, 710061, China.
Exp Cell Res. 2020 Nov 1;396(1):112286. doi: 10.1016/j.yexcr.2020.112286. Epub 2020 Sep 11.
Protein tyrosine phosphatase, nonreceptor type 13 (PTPN13), has emerged as a critical cancer-related gene that is implicated in a wide range of cancer types. However, the role of PTPN13 in clear cell renal cell carcinoma (ccRCC) is poorly understood. In the present study, we aimed to evaluate whether PTPN13 participates in the progression of ccRCC. Decreased expression of PTPN13 was found in ccRCC tissues, which predicted a shorter survival rate in ccRCC patients. PTPN13 expression was also lower in ccRCC cell lines, and the upregulation of PTPN13 repressed the proliferation, colony formation and invasion, but enhanced the apoptosis of ccRCC cells. In contrast, the silencing of PTPN13 produced the opposite effects. Further data showed that PTPN13 overexpression decreased the phosphorylation of Akt, while PTPN13 silencing increased the phosphorylation of Akt. Treatment with Akt inhibitor markedly abrogated the PTPN13 silencing-evoked oncogenic effect in ccRCC cells. Xenograft tumor experiments revealed that overexpression of PTPN13 remarkably restricted the tumor formation and growth of ccRCC cells in vivo associated with inactivation of Akt. In conclusion, our data demonstrated that overexpression of PTPN13 restricts the proliferation and invasion of ccRCC cells through inactivation of Akt. Our study suggests a tumor suppressive function of PTPN13 in ccRCC and highlights the potential role of PTPN13 in the progression of ccRCC.
蛋白酪氨酸磷酸酶，非受体型 13（PTPN13）已成为一种关键的癌症相关基因，涉及多种癌症类型。然而，PTPN13 在透明细胞肾细胞癌（ccRCC）中的作用知之甚少。在本研究中，我们旨在评估 PTPN13 是否参与 ccRCC 的进展。发现在 ccRCC 组织中 PTPN13 的表达降低，这预示着 ccRCC 患者的生存率较低。PTPN13 在 ccRCC 细胞系中的表达也较低，上调 PTPN13 抑制了 ccRCC 细胞的增殖、集落形成和侵袭，但增强了细胞凋亡。相反，沉默 PTPN13 则产生相反的效果。进一步的数据表明，PTPN13 过表达降低了 Akt 的磷酸化，而 PTPN13 沉默增加了 Akt 的磷酸化。Akt 抑制剂的处理显著阻断了 PTPN13 沉默在 ccRCC 细胞中引发的致癌作用。异种移植肿瘤实验表明，PTPN13 的过表达显著限制了体内 ccRCC 细胞的肿瘤形成和生长，同时 Akt 失活。总之，我们的数据表明，PTPN13 的过表达通过 Akt 的失活限制了 ccRCC 细胞的增殖和侵袭。我们的研究表明 PTPN13 在 ccRCC 中具有肿瘤抑制功能，并强调了 PTPN13 在 ccRCC 进展中的潜在作用。
