The fucosylated CD147 enhances the autophagy in epithelial ovarian cancer cells.

Mingbo Cai,Liancheng Zhu,Lu Deng,Juanjuan Liu,Mingzi Tan,Bei Lin,Jian Gao,Zhenhua Hu

doi:10.18632/oncotarget.13289

Abstract

Autophagy is modulated by multiple factors including CD147, but little is know about the effects and mechanism by which the modification of CD147 by Lewis y antigen regulates autophagy of ovarian cancer cell. Here, we reported that Lewis y antigen can promote basic autophagy activity and restrain autophagic cell death in ovarian cancer cells. Furthermore, human whole genome expression profile microarrays and massage pathway analysis revealed that during early stages of autophagy in ovarian cancer cells with highly expressing Lewis y antigen, PI3K/Akt-mTOR activity was reduced, in contrast, the PI3K/Akt-mTOR signaling pathway was activated as the length of amino acid deprivation increased, which inhibited eIF4G2 expression, further decreased the transcription of autophagy-related genes, suppressed autophagic cell death. we also elaborated that co-regulates protein degradation in cells via the ubiquitin-proteasome system and the autophagy-lysosome pathway. These findings suggested that the modification of CD147 by Lewis y antigen enhanced the survival ability by promoting basic autophagy activity and restraining autophagic cell death in ovarian cancer, thus playing an important role in ovarian cancer malignant progression.

Highlights

Due to its position, the ovary is difficult to image and monitor for abnormal growth; over 70% of patients with ovarian cancer are diagnosed at an advanced stage
Human whole genome expression profile microarrays and massage pathway analysis revealed that during early stages of autophagy in ovarian cancer cells with highly expressing Lewis y antigen, PI3K/Akt-mTOR activity was reduced, in contrast, the PI3K/Akt-mTOR signaling pathway was activated as the length of amino acid deprivation increased, which inhibited eIF4G2 expression, further decreased the transcription of autophagy-related genes, suppressed autophagic cell death. we elaborated that co-regulates protein degradation in cells via the ubiquitin-proteasome system and the autophagy-lysosome pathway
After shRNA-mediated downregulation of CD147 expression, changesof autophagic vacuole and cell morphology and rate of cell death within two group cells were observed using acridine orange (AO) stain and trypan blue experiment, the results indicated that, compared with the control shRNA group, autophagic vacuole reduced markedly and the cell death rate in CD147-shRNA transfected cells was significantly increased at 6 h, 12 h and 24 h after amino acid deprivation (Figure 1F, 1G)

Summary

Introduction

The ovary is difficult to image and monitor for abnormal growth; over 70% of patients with ovarian cancer are diagnosed at an advanced stage. Ovarian cancer has the highest mortality rate among all gynecological malignancies. It has been previously demonstrated that during the growth of malignant tumor cells, rapid proliferation can result in serious hypoxia and nutrient deficiencies in local tissues. Tumor cells can adapt to such harsh environmental changes by regulating their own metabolism, changing DNA repair, or inducing angiogenesis among other mechanisms [8, 31]. Ovarian cancer develops rapidly and adverse environmental changes including hypoxia, nutrition shortage, and inflammatory conditions predominate as the tumor becomes malignant. It is essential to explore the mechanisms by which ovarian cancer cells adapt to hypoxia and starvation in order to better control tumor progression

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Results

Conclusion