KIF4A drives gliomas growth by transcriptional repression of Rac1/Cdc42 to induce cytoskeletal remodeling in glioma cells

Zhang, Hui; Meng, Seng; Chu, Kun; Chu, Sufang; Fan, Yue-Chao; Bai, Jin; Yu, Zheng-Quan

doi:10.7150/jca.77238

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J Cancer 2022; 13(15):3640-3651. doi:10.7150/jca.77238 This issue Cite

Research Paper

KIF4A drives gliomas growth by transcriptional repression of Rac1/Cdc42 to induce cytoskeletal remodeling in glioma cells

Hui Zhang^1,4#, Seng Meng^2#, Kun Chu^2#, Sufang Chu², Yue-Chao Fan^4✉, Jin Bai^2,3✉, Zheng-Quan Yu^1✉

1. Department of Neurosurgery, the first Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
2. Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
3. Center of Clinical Oncology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
4. Department of Neurosurgery, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
#These authors contributed equally to this paper.

Citation:

Zhang H, Meng S, Chu K, Chu S, Fan YC, Bai J, Yu ZQ. KIF4A drives gliomas growth by transcriptional repression of Rac1/Cdc42 to induce cytoskeletal remodeling in glioma cells. J Cancer 2022; 13(15):3640-3651. doi:10.7150/jca.77238. https://www.jcancer.org/v13p3640.htm

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Abstract

Glioma is one of the most prevalent cancers diseases in the worldwide. Kinesin superfamily protein 4 (KIF4), a KIF member classified in Kinesin 4 has been indicated as a mediator acted in tumorigenesis of human cancer. However, the mechanism of KIF4A on glioma is yet to be investigated. This study aimed to explore the potential function and mechanism of KIF4A in gliomas. We analyzed the KIF4A expression and the prognosis in gliomas patients using The Cancer Genome Atlas (TCGA) databases. KIF4A level in normal human astrocyte cell (NHA) and glioma cell lines were examined by Western blot. We studied the function of KIF4A on proliferation, migration, invasion, cell cycle in glioma cell lines using a series of in vitro and in vivo experiments. Chromatin Immunoprecipitation (ChIP) analysis was applied to searching potential KIF4A related downstream in glioma. We identified the significant up-regulated expression of KIF4A both in glioma tissues and cell. Glioma patients with elevated KIF4A expression have shorter survival. Down-regulation of KIF4A exerted inhibitory effect on cell proliferation, invasion and migration. We crucially identified that KIF4A drives gliomas growth by transcriptional repression of Rac1/Cdc42 to induce cytoskeletal remodeling in glioma cells. Knockdown of KIF4A decreased RohA, Rac1, Cdc42, Pak1 and Pak2 expression level. Our study provided a prospect that KIF4A functions as an oncogene in glioma.

Keywords: Glioma, KIF4A, proliferation, metastasis, morphology, cytoskeletal

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APA

Zhang, H., Meng, S., Chu, K., Chu, S., Fan, Y.C., Bai, J., Yu, Z.Q. (2022). KIF4A drives gliomas growth by transcriptional repression of Rac1/Cdc42 to induce cytoskeletal remodeling in glioma cells. Journal of Cancer, 13(15), 3640-3651. https://doi.org/10.7150/jca.77238.

ACS

Zhang, H.; Meng, S.; Chu, K.; Chu, S.; Fan, Y.C.; Bai, J.; Yu, Z.Q. KIF4A drives gliomas growth by transcriptional repression of Rac1/Cdc42 to induce cytoskeletal remodeling in glioma cells. J. Cancer 2022, 13 (15), 3640-3651. DOI: 10.7150/jca.77238.

NLM

CSE

Zhang H, Meng S, Chu K, Chu S, Fan YC, Bai J, Yu ZQ. 2022. KIF4A drives gliomas growth by transcriptional repression of Rac1/Cdc42 to induce cytoskeletal remodeling in glioma cells. J Cancer. 13(15):3640-3651.

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