PBK promotes aggressive phenotypes of cervical cancer through ERK/c‐Myc signaling pathway

Hanlin Ma; Fang Han; Xiaohui Yan; Gonghua Qi; Yingwei Li; Rongrong Li; Shi Yan; Cunzhong Yuan; Kun Song; Beihua Kong

doi:10.1002/jcp.30134

journal article Nov 13, 2020

PBK promotes aggressive phenotypes of cervical cancer through ERK/c‐Myc signaling pathway

Hanlin Ma Fang Han

Xiaohui Yan

Gonghua Qi Yingwei Li

Journal of Cellular Physiology Vol. 236 No. 4 pp. 2767-2781 · Wiley

View at Publisher Save 10.1002/jcp.30134

Abstract

AbstractCervical cancer is the fourth most frequent cancer in women worldwide. PDZ‐binding kinase (PBK) is proven to promote the malignant behaviors of various carcinomas. However, its functional roles and oncogenic mechanisms in cervical cancer are poorly understood. In this study, we reported that PBK was highly expressed in cervical cancer tissues. PBK promoted the proliferation, metastasis, and cisplatin resistance of cervical cancer cells. OTS514, a specific PBK inhibitor, could significantly suppress proliferation and metastasis of cervical cancer cells in vitro and in a xenograft model. Besides, OTS514 could enhance cisplatin‐based chemosensitivity in cervical cancer cells. Mechanistically, PBK promoted the expression and stabilization of c‐Myc through phosphorylating ERK1/2. OTS514 suppressed the phosphorylation of ERK1/2 and the transcriptional activity of c‐Myc. Furthermore, inhibition of the ERK signal pathway by U0126 reversed the increased proliferation and metastasis induced by overexpression of PBK. Exogenous expression of c‐Myc counteracted the decreased proliferation and metastasis evoked by knockdown of PBK. In conclusion, PBK promoted the malignant progression of cervical cancer through ERK/c‐Myc signal pathway. PBK might be a promising molecular target for cervical cancer treatment.

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Details

Published: Nov 13, 2020
Vol/Issue: 236(4)
Pages: 2767-2781
License: View

Authors

H

Hanlin Ma

Department of Obstetrics and Gynecology Qilu Hospital of Shandong University Jinan China; Department of Oncology, Gynecologic Oncology Key Laboratory of Shandong Province Qilu Hospital of Shandong University Jinan China

F

Fang Han

Department of Ophthalmology Qilu Hospital of Shandong University Jinan China

X

Xiaohui Yan

Department of Infectious Diseases Binzhou People's Hospital Binzhou China

G

Gonghua Qi

Department of Obstetrics and Gynecology Qilu Hospital of Shandong University Jinan China

Y

Yingwei Li

Department of Obstetrics and Gynecology Qilu Hospital of Shandong University Jinan China; Department of Cell Biology, Cheeloo College of Medicine Shandong University Jinan China

R

Rongrong Li

Department of Obstetrics and Gynecology Qilu Hospital of Shandong University Jinan China; Department of Oncology, Gynecologic Oncology Key Laboratory of Shandong Province Qilu Hospital of Shandong University Jinan China

S

Shi Yan

Department of Obstetrics and Gynecology Qilu Hospital of Shandong University Jinan China; Department of Oncology, Gynecologic Oncology Key Laboratory of Shandong Province Qilu Hospital of Shandong University Jinan China

C

Cunzhong Yuan

Department of Obstetrics and Gynecology Qilu Hospital of Shandong University Jinan China; Department of Oncology, Gynecologic Oncology Key Laboratory of Shandong Province Qilu Hospital of Shandong University Jinan China

K

Kun Song

Department of Obstetrics and Gynecology Qilu Hospital of Shandong University Jinan China; Department of Oncology, Gynecologic Oncology Key Laboratory of Shandong Province Qilu Hospital of Shandong University Jinan China

B

Beihua Kong

Department of Obstetrics and Gynecology Qilu Hospital of Shandong University Jinan China; Department of Oncology, Gynecologic Oncology Key Laboratory of Shandong Province Qilu Hospital of Shandong University Jinan China

Cite This Article

Hanlin Ma, Fang Han, Xiaohui Yan, et al. (2020). PBK promotes aggressive phenotypes of cervical cancer through ERK/c‐Myc signaling pathway. Journal of Cellular Physiology, 236(4), 2767-2781. https://doi.org/10.1002/jcp.30134

PBK promotes aggressive phenotypes of cervical cancer through ERK/c‐Myc signaling pathway

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