ApoM suppresses kidney renal clear cell carcinoma growth and metastasis via the Hippo-YAP signaling pathway.
ApoM suppresses kidney renal clear cell carcinoma growth and metastasis via the Hippo-YAP signaling pathway.
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DOI：
10.1016/j.abb.2023.109642
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发表时间：
2023-05
影响因子：
3.9
通讯作者：
Ting Xu;D. Wei;Zhe Yang;Shanghuang Xie;Zhangbin Yan;Cong Chen;Wenxin Hu;Zhida Shi;
中科院分区：
文献类型：
--
作者：
Ting Xu;D. Wei;Zhe Yang;Shanghuang Xie;Zhangbin Yan;Cong Chen;Wenxin Hu;Zhida Shi;
肾细胞癌是世界范围内最常见的恶性肿瘤之一，肾透明细胞癌(KIRC)是肾细胞癌中最常见的组织病理学类型。然而，KIRC进展的机制仍然知之甚少。载脂蛋白M(ApoM)是一种血浆载脂蛋白，是脂转运蛋白超家族的成员。脂质代谢是肿瘤进展的关键，其相关蛋白可作为肿瘤的治疗靶点。载脂蛋白可以影响几种癌症的发展，但它与KIRC的关系尚不清楚。本研究旨在研究载脂蛋白在KIRC中的生物学功能，并揭示其潜在的分子机制。我们发现载脂蛋白在KIRC中的表达显著降低，并且与患者的预后密切相关。APOM过表达显著抑制KIRC细胞体外增殖，抑制KIRC细胞上皮间充质转化(EMT)，降低其转移能力。此外，体内过表达apom可抑制KIRC细胞的生长。此外，我们还发现apom在KIRC中的过表达降低了Hippo-Yap蛋白的表达和YAP的稳定性，从而抑制了KIRC的生长和进展。因此，apom可能成为治疗KIRC的潜在靶点。
Renal cell carcinoma is one of the most common malignancies worldwide, and kidney renal clear cell carcinoma (KIRC) is the most common histopathological type of renal cell carcinoma. However, the mechanism of KIRC progression remains poorly understood. Apolipoprotein M (ApoM) is a plasma apolipoprotein and a member of the lipid transport protein superfamily. Lipid metabolism is essential for tumor progression, and its related proteins can be used as therapeutic targets for tumors. ApoM influences the development of several cancers, but its relationship with KIRC remains unclear. In this study, we aimed to investigate the biological function of ApoM in KIRC and to reveal its potential molecular mechanisms. We found that ApoM expression was significantly reduced in KIRC and was strongly correlated with patient prognosis. ApoM overexpression significantly inhibited KIRC cell proliferation in vitro, suppressed the epithelial mesenchymal transition (EMT) of KIRC cells, and decreased their metastatic capacity. Additionally, the growth of KIRC cells was inhibited by ApoM overexpression in vivo. In addition, we found that overexpression of ApoM in KIRC attenuated Hippo-YAP protein expression and YAP stability and thus inhibited KIRC growth and progression. Therefore, ApoM may be a potential target for the treatment of KIRC.