Research Papers:

A novel miR-34a target, protein kinase D1, stimulates cancer stemness and drug resistance through GSK3/β-catenin signaling in breast cancer

Do Yeon Kim _, Eun Young Park, EunSun Chang, Hyeok-Gu Kang, Yoonjin Koo, Eun Ji Lee, Je Yeong Ko, Hyun Kyung Kong, Kyung-Hee Chun and Jong Hoon Park

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Oncotarget. 2016; 7:14791-14802. https://doi.org/10.18632/oncotarget.7443

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Do Yeon Kim1,, Eun Young Park1,, EunSun Chang1, Hyeok-Gu Kang2,3, Yoonjin Koo1, Eun Ji Lee1, Je Yeong Ko1, Hyun Kyung Kong1, Kyung-Hee Chun2,3, Jong Hoon Park1

1Department of Biological Science, Sookmyung Women’s University, Seoul, Republic of Korea

2Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Republic of Korea

3Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea

These authors contributed equally to this work

Correspondence to:

Jong Hoon Park, e-mail: [email protected]

Keywords: miR-34a, PRKD1, β-catenin signaling, cancer stemness, drug resistance

Received: November 05, 2015     Accepted: January 31, 2016     Published: February 17, 2016


One of the properties of human breast cancer cells is cancer stemness, which is characterized by self-renewal capability and drug resistance. Protein kinase D1 (PRKD1) functions as a key regulator of many cellular processes and is downregulated in invasive breast cancer cells. In this study, we found that PRKD1 was upregulated in MCF-7-ADR human breast cancer cells characterized by drug resistance. Additionally, we discovered that PRKD1 expression was negatively regulated by miR-34a binding to the PRKD1 3′-UTR. PRKD1 expression increased following performance of a tumorsphere formation assay in MCF-7-ADR cells. We also found that reduction of PRKD1 by ectopic miR-34a expression or PRKD1 siRNA treatment resulted in suppressed self-renewal ability in breast cancer stem cells. Furthermore, we confirmed that the PRKD1 inhibitor CRT0066101 reduced phosphorylated PKD/PKCμ, leading to suppression of breast cancer stemness through GSK3/β-catenin signaling. PRKD1 inhibition also influenced apoptosis initiation in MCF-7-ADR cells. Tumors from nude mice treated with miR-34a or CRT0066101 showed suppressed tumor growth, proliferation, and induced apoptosis. These results provide evidence that regulation of PRKD1, a novel miR-34a target, contributes to overcoming cancer stemness and drug resistance in human breast cancer.

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