Int J Biol Sci 2020; 16(15):2835-2852. doi:10.7150/ijbs.46285 This issue Cite

Research Paper

Rictor promotes cell migration and actin polymerization through regulating ABLIM1 phosphorylation in Hepatocellular Carcinoma

Xin Dong1, Mei Feng1,2, Hui Yang1, Hengkang Liu1, Hua Guo5, Xianshu Gao3, Yucun Liu2, Rong Liu1, Ning Zhang1, Ruibing Chen4✉, Ruirui Kong1✉

1. Translational Cancer Research Center, Peking University First Hospital, Beijing. 100034, P.R. China.
2. Department of General Surgery, Peking University First Hospital, Beijing. 100034, P.R. China.
3. Department of Radiation Oncology, Peking University First Hospital, Beijing. 100034, P.R. China.
4. School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, P.R. China.
5. Laboratory of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, P.R. China.

Citation:
Dong X, Feng M, Yang H, Liu H, Guo H, Gao X, Liu Y, Liu R, Zhang N, Chen R, Kong R. Rictor promotes cell migration and actin polymerization through regulating ABLIM1 phosphorylation in Hepatocellular Carcinoma. Int J Biol Sci 2020; 16(15):2835-2852. doi:10.7150/ijbs.46285. https://www.ijbs.com/v16p2835.htm
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Abstract

Graphic abstract

As one of the most ominous malignancies, hepatocellular carcinoma (HCC) is frequently diagnosed at an advanced stage, owing to its aggressive invasion and metastatic spread. Emerging evidence has demonstrated that Rictor, as a unique component of the mTORC2, plays a role in cell migration, as it is dysregulated in various cancers, including HCC. However, the underlying molecular mechanism has not been well-characterized. Here, evaluation on a tissue-array panel and bioinformatics analysis revealed that Rictor is highly expressed in HCC tissues. Moreover, increased Rictor expression predicts poor survival of HCC patients. Rictor knockdown significantly suppressed cell migration and actin polymerization, thereby leading to decreased nuclear accumulation of MKL1 and subsequent inactivation of SRF/MKL1-dependent gene transcription, i.e. Arp3 and c-Fos. Mechanistically, we identified ABLIM1 as a previously unknown phosphorylation target of Rictor. Rictor interacts with ABLIM1 and regulates its serine phosphorylation in HCC cells. We generated ABLIM1 knockout cell lines of HCC, in which dominant negative mutations of Ser 214 and Ser 431 residues inhibited the ABLIM1-mediated actin polymerization and the MKL1 signaling pathway. Overall, ABLIM1 phosphorylation induced by Rictor plays an important role in controlling actin polymerization in HCC cells.

Keywords: hepatocellular carcinoma, Rictor, ABLIM1, phosphorylation, actin polymerization


Citation styles

APA
Dong, X., Feng, M., Yang, H., Liu, H., Guo, H., Gao, X., Liu, Y., Liu, R., Zhang, N., Chen, R., Kong, R. (2020). Rictor promotes cell migration and actin polymerization through regulating ABLIM1 phosphorylation in Hepatocellular Carcinoma. International Journal of Biological Sciences, 16(15), 2835-2852. https://doi.org/10.7150/ijbs.46285.

ACS
Dong, X.; Feng, M.; Yang, H.; Liu, H.; Guo, H.; Gao, X.; Liu, Y.; Liu, R.; Zhang, N.; Chen, R.; Kong, R. Rictor promotes cell migration and actin polymerization through regulating ABLIM1 phosphorylation in Hepatocellular Carcinoma. Int. J. Biol. Sci. 2020, 16 (15), 2835-2852. DOI: 10.7150/ijbs.46285.

NLM
Dong X, Feng M, Yang H, Liu H, Guo H, Gao X, Liu Y, Liu R, Zhang N, Chen R, Kong R. Rictor promotes cell migration and actin polymerization through regulating ABLIM1 phosphorylation in Hepatocellular Carcinoma. Int J Biol Sci 2020; 16(15):2835-2852. doi:10.7150/ijbs.46285. https://www.ijbs.com/v16p2835.htm

CSE
Dong X, Feng M, Yang H, Liu H, Guo H, Gao X, Liu Y, Liu R, Zhang N, Chen R, Kong R. 2020. Rictor promotes cell migration and actin polymerization through regulating ABLIM1 phosphorylation in Hepatocellular Carcinoma. Int J Biol Sci. 16(15):2835-2852.

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