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Novel Functions of CD147 in the Mitochondria Exacerbates Melanoma Metastasis
International Journal of Biological Sciences ( IF 9.2 ) Pub Date : 2021-1-1 , DOI: 10.7150/ijbs.52043
Lixia Lu 1, 2, 3 , Jianglin Zhang 1, 2, 3 , Pingping Gan 4 , Lisha Wu 1, 2, 3 , Xu Zhang 1, 2, 3 , Cong Peng 1, 2, 3 , Jianda Zhou 5 , Xiang Chen 1, 2, 3 , Juan Su 1, 2, 3
Affiliation  

Melanoma is an aggressive form of skin cancer characterized by rapid invasion and metastasis. CD147 is known to be functioning in cell invasion. In this study, we showed that CD147 was translocated from the cell membrane to the mitochondria in advanced melanoma. Melanoma patients with CD147 localized to the mitochondria confer a worse prognosis. The mitochondrial CD147 levels are correlated with the invasion potential of various melanoma cell lines as well as mitochondrial energy metabolism. Depletion of CD147 decreased the activity of mitochondrial complex V. STRING analysis for protein-protein interaction networks (PPIN) in CD147-depleted melanoma cells showed that mitochondrial proteins HSP60 and ATP5B, a subunit of mitochondrial complex V, were node proteins. HSP60 upregulation was correlated with a worse prognosis of melanoma patients. Co-immunoprecipitation (Co-IP) assay indicates that CD147 interacts with HSP60. These data suggested that mitochondrial CD147 may prompt HSP60 to activate ATP5B, thereby promoting the mitochondrial aerobic oxidation and the invasive abilities of melanoma cells. Correlation analysis of the data acquired from patients was helpful to draw a 5-year survival curve for patients who screened positive and negative for mitochondrial CD147. This study unravels the function of CD147 in tumor invasion and highlights it as a potential tumor therapeutic target.

中文翻译:

CD147 在线粒体中的新功能会加剧黑色素瘤的转移

黑色素瘤是一种侵袭性皮肤癌,其特征是快速侵袭和转移。已知 CD147 在细胞侵袭中起作用。在这项研究中,我们发现 CD147 在晚期黑色素瘤中从细胞膜转移到线粒体。CD147 定位于线粒体的黑色素瘤患者预后较差。线粒体 CD147 水平与各种黑色素瘤细胞系的侵袭潜力以及线粒体能量代谢相关。CD147 的消耗降低了线粒体复合物 V 的活性。在 CD147 耗尽的黑色素瘤细胞中对蛋白质-蛋白质相互作用网络 (PPIN) 的 STRING 分析表明,线粒体蛋白 HSP60 和 ATP5B(线粒体复合物 V 的一个亚基)是节点蛋白。HSP60 上调与黑色素瘤患者的预后较差相关。免疫共沉淀 (Co-IP) 分析表明 CD147 与 HSP60 相互作用。这些数据表明线粒体CD147可能促使HSP60激活ATP5B,从而促进线粒体有氧氧化和黑色素瘤细胞的侵袭能力。对从患者获得的数据进行相关分析有助于绘制线粒体 CD147 筛查阳性和阴性患者的 5 年生存曲线。这项研究揭示了 CD147 在肿瘤侵袭中的作用,并强调它是一个潜在的肿瘤治疗靶点。对从患者获得的数据进行相关分析有助于绘制线粒体 CD147 筛查阳性和阴性患者的 5 年生存曲线。这项研究揭示了 CD147 在肿瘤侵袭中的作用,并强调它是一个潜在的肿瘤治疗靶点。对从患者获得的数据进行相关分析有助于绘制线粒体 CD147 筛查阳性和阴性患者的 5 年生存曲线。这项研究揭示了 CD147 在肿瘤侵袭中的作用,并强调它是一个潜在的肿瘤治疗靶点。
更新日期:2021-01-01
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