Relevance of mortalin to cancer cell stemness and cancer therapy.
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.
Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsinmi-ro, Seongdong-gu, Seoul, Republic of Korea.
Chae-Ok
CO
Yun
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.|Graduate School of Life &Environmental Sciences, University of Tsukuba, Ibaraki- 305-8575, Japan.
Priyanshu
P
Bhargava
Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsinmi-ro, Seongdong-gu, Seoul, Republic of Korea.
Youjin
Y
Na
Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsinmi-ro, Seongdong-gu, Seoul, Republic of Korea.
Jung-Sun
JS
Lee
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.
Jihoon
J
Ryu
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.
Sunil C
SC
Kaul
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.
Renu
R
Wadhwa
D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000502:physiology; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D034741:RNA, Small Interfering; D013844:Thiazoles / Q000494:pharmacology; D015854:Up-Regulation
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002109:Caffeic Acids; D018840:HSP70 Heat-Shock Proteins; D011725:Pyridines; D034741:RNA, Small Interfering; D013844:Thiazoles; C080352:mortalin; C097880:MKT 077; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol