Autophagy promotes invadopodia formation in human ovarian cancer cells via the p62-extracellular signal-regulated kinase 1/2 pathway

Zhou,Zizhen; Zhao,Jia; Liu,Yanan; Yan,Xiaoyu; Sun,Hongyu; Xia,Meihui; Su,Jing

doi:10.3892/etm.2021.10384

Autophagy promotes invadopodia formation in human ovarian cancer cells via the p62-extracellular signal-regulated kinase 1/2 pathway

Authors:
- Zizhen Zhou
- Jia Zhao
- Yanan Liu
- Xiaoyu Yan
- Hongyu Sun
- Meihui Xia
- Jing Su
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Affiliations: Key Laboratory of Pathobiology, Ministry of Education, Department of Pathophysiology, Basic College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Obstetrics and Gynecology, The First Hospital, Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: July 5, 2021 https://doi.org/10.3892/etm.2021.10384
Article Number: 952
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Invasiveness and metastatic potential are among the most essential characteristics of malignant tumors. Furthermore, it has been reported that autophagy and invasion are enhanced when tumor cells are grown in adverse conditions, such as nutritional deficiency and starvation. However, the association between autophagy and invasion remains largely unclear. In the present study, Earle's balanced salt solution (EBSS) was used to induce autophagy and an autophagy inhibitor was used to block autophagy. The results of Transwell assays revealed that autophagy inhibition limited the invasiveness of human ovarian cancer cells. Furthermore, the results of invadopodia formation assay indicated that autophagy stimulated invadopodia formation, and the selective autophagy receptor and signaling adaptor, sequestosome-1 (SQSTM1/p62 or simply p62), was closely associated with invadopodia formation in human ovarian cancer SKOV3 cells. The results of western blot analysis indicated that autophagy induced changes in p62 protein levels and p62 then functioned as a negative regulator of extracellular signal-regulated kinase 1/2 (ERK1/2) activity and invadopodia formation. The interaction between autophagy and invasion may thus be a self-protective mechanism for tumor cells in an unfavorable environment of nutritional deficiency, that maintains their survival and leads to increased invasiveness. An exploration of the intrinsic link between autophagy and invasion may provide a novel theoretical basis to reverse the resistance of tumor cells to a nutritional deficient environment.

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