Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsinmi-ro, Seongdong-gu, Seoul, Republic of Korea.
DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Biomedical Research Institute, National Institute of Advanced Industrial Science &Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba - 305 8565, Japan.
Sci Rep. 2017 Feb 6;7:42016. doi: 10.1038/srep42016.
Mortalin/mtHsp70 is a member of Hsp70 family of proteins. Enriched in a large variety of cancers, it has been shown to contribute to the process of carcinogenesis by multiple ways including inactivation of tumor suppressor p53 protein, deregulation of apoptosis and activation of EMT signaling. In this study, we report that upregulation of mortalin contributes to cancer cell stemness. Several cancer cell stemness markers, such as ABCG2, OCT-4, CD133, ALDH1, CD9, MRP1 and connexin were upregulated in mortalin-overexpressing cells that showed higher ability to form spheroids. These cells also showed higher migration, and were less responsive to a variety of cancer chemotherapeutic drugs. Of note, knockdown of mortalin by specific shRNA sensitized these cells to all the drugs used in this study. We report that low doses of anti-mortalin molecules, MKT-077 and CAPE, also caused similar sensitization of cancer cells to chemotherapeutic drugs and hence are potential candidates for effective cancer chemotherapy.
线粒体热休克蛋白 70（mortalin/mtHsp70）是热休克蛋白 70 家族的一员。它在多种癌症中丰富表达，已被证明通过多种方式促进癌发生过程，包括肿瘤抑制蛋白 p53 的失活、凋亡的失调和 EMT 信号的激活。在这项研究中，我们报告了 mortalin 的上调有助于癌细胞的干性。在过表达 mortalin 的细胞中，几种癌细胞干性标志物，如 ABCG2、OCT-4、CD133、ALDH1、CD9、MRP1 和连接蛋白上调，这些细胞具有更高的形成球体的能力。这些细胞还表现出更高的迁移能力，对多种癌症化疗药物的反应性降低。值得注意的是，特异性 shRNA 敲低 mortalin 可使这些细胞对本研究中使用的所有药物敏感。我们报告说，低剂量的抗 mortalin 分子 MKT-077 和 CAPE 也可使癌细胞对化疗药物产生类似的增敏作用，因此它们是有效癌症化疗的潜在候选药物。
