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PP2A 通过降低 Hippo 信号通路驱动结直肠癌细胞的干性。

PP2A drives the stemness in colorectal cancer cells by decreasing the Hippo signaling pathway.

机构信息

Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University & The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, 610031, China.

Department of Anorectal, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University & The Second Affiliated Hospital of Chengdu, Chongqing Medical University, Chengdu, 610031, China.

出版信息

Cell Mol Biol (Noisy-le-grand). 2023 Dec 20;69(14):114-120. doi: 10.14715/cmb/2023.69.14.18.

Abstract

Colorectal cancer (CRC) is one of the most prevalent malignancies. Accumulating evidence suggests that Hippo signaling pathway is a crucial signaling pathway that regulates stemness in multiple cancers, including CRC. Given that, the therapeutics targeting the Hippo pathway are of great interest. At the same time, previous studies have reported that PP2A regulates the Hippo pathway in tumorigenesis. In this study, we uncover the role of PP2A in vitro and in vivo and the interaction between PP2A and Hippo signaling pathway in CRC stemness. We investigate the molecular mechanism of PP2A-mediated Hippo pathway in CRC progression from the aspect of cell stemness. Furthermore, we explore the transcription factor of PP2A in CRC. In view of circRNA's regulation of cancer-related signaling pathways in CRC, we also study the association between PP2A-mediated Hippo pathway and the CRC-related circRNA (hsa-circ-001680) confirmed in previous studies. Of note, we demonstrate how hsa-circ-001680 regulates PP2A expression. The effect of hsa-circ-001680 on PP2A stability is investigated as well. In conclusion, the study demonstrates the mechanism of PP2A-mediated pathway on CRC stemness, which may provide new sights for the treatment of CRC.

摘要

结直肠癌(CRC)是最常见的恶性肿瘤之一。越来越多的证据表明,Hippo 信号通路是调节多种癌症包括 CRC 干性的关键信号通路。鉴于此,靶向 Hippo 通路的治疗方法具有很大的研究价值。同时,先前的研究已经报道 PP2A 在肿瘤发生中调节 Hippo 通路。在本研究中,我们揭示了 PP2A 在体外和体内的作用以及在 CRC 干性中 PP2A 和 Hippo 信号通路之间的相互作用。我们从细胞干性的角度研究了 PP2A 介导的 Hippo 通路在 CRC 进展中的分子机制。此外,我们还研究了 CRC 中 PP2A 的转录因子。鉴于 circRNA 在 CRC 中对癌症相关信号通路的调节作用,我们还研究了之前研究中证实的 PP2A 介导的 Hippo 通路与 CRC 相关 circRNA(hsa-circ-001680)之间的关联。值得注意的是,我们展示了 hsa-circ-001680 如何调节 PP2A 的表达。还研究了 hsa-circ-001680 对 PP2A 稳定性的影响。总之,该研究阐明了 PP2A 介导的通路在 CRC 干性中的作用机制,这可能为 CRC 的治疗提供新的思路。

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