STK39 is a novel kinase contributing to the progression of hepatocellular carcinoma by the PLK1/ERK signaling pathway

Zhang, Chengfei; Wang, Xiaoming; Fang, Dan; Xu, Ping; Mo, Xiao; Hu, Chao; Abdelatty, Alaa; Wang, Mei; Xu, Haojun; Sun, Qi; Zhou, Guoren; She, Junjun; Xia, Jinglin; Hui, Kam Man; Xia, Hongping

doi:10.7150/thno.48112

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Nanotheranostics 2024; 8(4): 442-457. [Abstract] [Full text] [PDF]

Nanotheranostics 2024; 8(4): 427-441. [Abstract] [Full text] [PDF]

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Theranostics 2021; 11(5):2108-2122. doi:10.7150/thno.48112 This issue Cite

Research Paper

STK39 is a novel kinase contributing to the progression of hepatocellular carcinoma by the PLK1/ERK signaling pathway

Chengfei Zhang^1,3#, Xiaoming Wang^2#, Dan Fang^1#, Ping Xu¹, Xiao Mo¹, Chao Hu¹, Alaa Abdelatty¹, Mei Wang¹, Haojun Xu¹, Qi Sun¹, Guoren Zhou^3✉, Junjun She^4✉, Jinglin Xia^5✉, Kam Man Hui^6✉, Hongping Xia^1,3,4,6✉

1. Department of Pathology, School of Basic Medical Sciences & Sir Run Run Hospital & State Key Laboratory of Reproductive Medicine & Key Laboratory of Antibody Technique of National Health Commission, Nanjing Medical University, Nanjing 211166, Jiangsu, China.
2. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, Anhui, China.
3. Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research, Nanjing 210009, Jiangsu, China.
4. Department of High Talent & General Surgery & Med-X Institute, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, 710061, Shaanxi, China.
5. The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China.
6. Laboratory of Cancer Genomics, National Cancer Centre Singapore & Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore.
#These authors contributed equally to this work.

Citation:

Zhang C, Wang X, Fang D, Xu P, Mo X, Hu C, Abdelatty A, Wang M, Xu H, Sun Q, Zhou G, She J, Xia J, Hui KM, Xia H. STK39 is a novel kinase contributing to the progression of hepatocellular carcinoma by the PLK1/ERK signaling pathway. Theranostics 2021; 11(5):2108-2122. doi:10.7150/thno.48112. https://www.thno.org/v11p2108.htm

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Abstract

Rationale: Protein kinases are critical therapeutic targets for curing hepatocellular carcinoma (HCC). As a serine/threonine kinase, the potential roles of serine/threonine kinase 39 (STK39) in HCC remain to be explored.

Methods: The expression of STK39 was examined by RT-qPCR, western blotting and immunohistochemistry. Cell proliferation and apoptosis were detected by CCK8 and TUNEL kit. Cell migration and invasion assays were performed using a transwell system with or without Matrigel. RNA-seq, mass spectrometry and luciferase reporter assays were used to identify STK39 binding proteins.

Results: Here, we firstly report that STK39 was highly overexpressed in clinical HCC tissues compared with adjacent tissues, high expression of STK39 was induced by transcription factor SP1 and correlated with poor patient survival. Gain and loss of function assays revealed that overexpression of STK39 promoted HCC cell proliferation, migration and invasion. In contrast, the depletion of STK39 attenuated the growth and metastasis of HCC cells. Moreover, knockdown of STK39 induced the HCC cell cycle arrested in the G2/M phase and promoted apoptosis. In mechanistic studies, RNA-seq revealed that STK39 positively regulated the ERK signaling pathway. Mass spectrometry identified that STK39 bound to PLK1 and STK39 promoted HCC progression and activated ERK signaling pathway dependent on PLK1.

Conclusions: Thus, our study uncovers a novel role of STK39/PLK1/ERK signaling axis in the progress of HCC and suggests STK39 as an indicator for prognosis and a potential drug target of HCC.

Keywords: STK39, PLK1, ERK, HCC, proliferation

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APA

Zhang, C., Wang, X., Fang, D., Xu, P., Mo, X., Hu, C., Abdelatty, A., Wang, M., Xu, H., Sun, Q., Zhou, G., She, J., Xia, J., Hui, K.M., Xia, H. (2021). STK39 is a novel kinase contributing to the progression of hepatocellular carcinoma by the PLK1/ERK signaling pathway. Theranostics, 11(5), 2108-2122. https://doi.org/10.7150/thno.48112.

ACS

Zhang, C.; Wang, X.; Fang, D.; Xu, P.; Mo, X.; Hu, C.; Abdelatty, A.; Wang, M.; Xu, H.; Sun, Q.; Zhou, G.; She, J.; Xia, J.; Hui, K.M.; Xia, H. STK39 is a novel kinase contributing to the progression of hepatocellular carcinoma by the PLK1/ERK signaling pathway. Theranostics 2021, 11 (5), 2108-2122. DOI: 10.7150/thno.48112.

NLM

CSE

Zhang C, Wang X, Fang D, Xu P, Mo X, Hu C, Abdelatty A, Wang M, Xu H, Sun Q, Zhou G, She J, Xia J, Hui KM, Xia H. 2021. STK39 is a novel kinase contributing to the progression of hepatocellular carcinoma by the PLK1/ERK signaling pathway. Theranostics. 11(5):2108-2122.

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