FBXO22 Promotes Growth and Metastasis and Inhibits Autophagy in Epithelial Ovarian Cancers via the MAPK/ERK Pathway

Abstract

E3 ubiquitin ligase F-box only protein 22 (FBXO22), which targets the key regulators of cellular activities for ubiquitylation and degradation, plays an important role in tumorigenesis and metastasis. However, the function of FBXO22 in epithelial ovarian cancers has not been reported. This study aims to explore the biological function of FBXO22 in epithelial ovarian cancers progression and metastasis and its specific regulation mechanism. Immunohistochemistry analysis of tissue microarray was performed to evaluate the expression of FBXO22 in epithelial ovarian cancers patients. The proliferative ability of epithelial ovarian cancers cells was examined by the CCK8. The metastasis ability was detected by the wound healing assay, migration and invasion assays. Western blot was used to verify the relationship between FBXO22 expression and mitogen-activated protein kinase related proteins. Autophagic flux was detected by electron microscopy, mRFP-GFP-LC3 adenovirus, lysosomal tracker and western blot. For in vivo experiments, the effect of FBXO22 on epithelial ovarian cancers resistance was observed in a xenograft tumor model and a metastatic mice model. We found that FBXO22 expression was significantly increased in epithelial ovarian cancers tissues and was closely correlated with clinical pathological factors. As a result, we found that FBXO22 promoted the growth and metastasis, as well as inhibited the autophagy flux. In addition, we identified that FBXO22 performed these functions via the MAPK/ERK pathway. Our results first reported the function of FBXO22 in epithelial ovarian cancer and the correlation between FBXO22 and autophagy, suggesting FBXO22 as a novel target of epithelial ovarian cancers assessment and treatment.

Role of autophagy and its regulation by noncoding RNAs in ovarian cancer

“…47,48 During tumorigenesis, the oncogenes FBXO22 and PKP3 are overexpressed in OC cells and promote tumor invasion and metastasis by inhibiting autophagy via the MAPK pathway. 49,50 The MAPK/ERK pathway is also associated with cisplatin resistance in OC and can be further modulated by STAT3 and p53 signaling. 51 Treatment with MAPK inhibitors suppresses cell growth and migration by inducing autophagic death in OC cells.…”

Green Tea Epigallocatechin-3-Gallate Regulates Autophagy in Male and Female Reproductive Cancer

“…Moreover, the downregulation of p-ERK1/2 protein via the MAPK/ERK pathway induced early autophagy and apoptosis for anti-tumor activities in breast and cervical cancer ( Hanyu et al, 2020 ; Liu et al, 2020 ). On the contrary, the promotion of MAPK/ERK pathway was shown to inhibit autophagy on promoting metastasis ( Li et al, 2021 ).…”