J Cancer 2023; 14(15):2759-2770. doi:10.7150/jca.84687 This issue Cite

Research Paper

ANP32A Knockdown Attenuates the Malignant Biological Behavior of Colorectal Cancer Cells by Suppressing Epithelial-mesenchymal Transition and ERK Activation

Xiaojuan Li1*, Xumei Li1*, Guoxiang Liu1, Luwei Zhou1, Yisa Liu1, Tong Dou1,5, Xu Chen1✉, Juan Wang2,3,4✉

1. Department of Pharmacy, Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region 541199, China.
2. Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region 541001, China.
3. Guangxi Health Commission Key Laboratory of Basic Research in Sphingolipid Metabolism Related Diseases, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region 541001, China.
4. Faculty of Basic Medicine, Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region 541004, China.
5. School of Pharmacy, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.
*Contributed equally.

Citation:
Li X, Li X, Liu G, Zhou L, Liu Y, Dou T, Chen X, Wang J. ANP32A Knockdown Attenuates the Malignant Biological Behavior of Colorectal Cancer Cells by Suppressing Epithelial-mesenchymal Transition and ERK Activation. J Cancer 2023; 14(15):2759-2770. doi:10.7150/jca.84687. https://www.jcancer.org/v14p2759.htm
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Abstract

Graphic abstract

Acidic leucine rich nuclear phosphoprotein-32A (ANP32A) protein has a variety of functions, such as regulating cell differentiation, influencing cell apoptosis and cell cycle progression. Our previous study demonstrated that high expression of ANP32A was found in the tumor tissues of colorectal cancer (CRC) patients and was positively associated with tumor grading. However, the function and underlying mechanisms of ANP32A in CRC metastasis have not been fully explored. In this study, we found that ANP32A knockdown significantly attenuated the migration and invasion, and epithelial-mesenchymal transition (EMT) in cells. Further mechanistic studies revealed that ANP32A knockdown inhibited the expression of β-catenin and phosphorylated-ERK. The immunofluorescent staining experiment has revealed that ANP32A was expressed in the cell membrane, cytosol and nucleus, and its expression was positively associated with β-catenin expression levels. Moreover, the ability of cell migration and invasion was inhibited, the expression of E-cadherin was enhanced following ANP32A knockdown, and these affects were abolished by an ERK activator PMA, enhanced by an ERK inhibitor PD98059. Moreover, our animal experiment also demonstrated that silenced ANP32A inhibited CRC cell growth, multi-organ metastasis, ERK activation and EMT progression in vivo. Collectively, these findings demonstrated that ANP32A promotes CRC progression and that may be a promising target for the anti-metastasis treatment of CRC.

Keywords: Acidic leucine rich nuclear phosphoprotein-32A, metastasis, epithelial-mesenchymal transition, β-catenin, ERK, colorectal cancer


Citation styles

APA
Li, X., Li, X., Liu, G., Zhou, L., Liu, Y., Dou, T., Chen, X., Wang, J. (2023). ANP32A Knockdown Attenuates the Malignant Biological Behavior of Colorectal Cancer Cells by Suppressing Epithelial-mesenchymal Transition and ERK Activation. Journal of Cancer, 14(15), 2759-2770. https://doi.org/10.7150/jca.84687.

ACS
Li, X.; Li, X.; Liu, G.; Zhou, L.; Liu, Y.; Dou, T.; Chen, X.; Wang, J. ANP32A Knockdown Attenuates the Malignant Biological Behavior of Colorectal Cancer Cells by Suppressing Epithelial-mesenchymal Transition and ERK Activation. J. Cancer 2023, 14 (15), 2759-2770. DOI: 10.7150/jca.84687.

NLM
Li X, Li X, Liu G, Zhou L, Liu Y, Dou T, Chen X, Wang J. ANP32A Knockdown Attenuates the Malignant Biological Behavior of Colorectal Cancer Cells by Suppressing Epithelial-mesenchymal Transition and ERK Activation. J Cancer 2023; 14(15):2759-2770. doi:10.7150/jca.84687. https://www.jcancer.org/v14p2759.htm

CSE
Li X, Li X, Liu G, Zhou L, Liu Y, Dou T, Chen X, Wang J. 2023. ANP32A Knockdown Attenuates the Malignant Biological Behavior of Colorectal Cancer Cells by Suppressing Epithelial-mesenchymal Transition and ERK Activation. J Cancer. 14(15):2759-2770.

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