Abstract
PD-L1 is a well-known immune co-stimulatory molecule that regulates tumour cell escape from immunity by suppressing the immune response. However, the clinical significance of PD-L1 in the progression of ovarian cancer is unclear. Our study demonstrated that PD-L1 is up-regulated in ovarian tumour tissue compared with its expression level in adjacent normal tissue. Furthermore, we confirmed that PD-L1 increases the proliferation of cancer cells by activating the AKT-mTORC signalling pathway, which is also enhanced by the expression of S6K, the substrate of mTORC. In addition, PD-L1 promotes the autophagy of ovarian cancer cells by up-regulating the expression of BECN1, a crucial molecule involved in the regulation of autophagy. In conclusion, PD-L1 may provide a target for the development of a novel strategy for the treatment of ovarian cancer.
Highlights
Ovarian cancer (OC) is one of the most common malignant tumours in women, and its mortality rate ranks first among gynaecological tumours [1,2]
Preclinical studies demonstrated that AKT is activated frequently in OC, resulting in over-activation of AKT signalling cascades, including migration or invasion, proliferation, apoptosis, survival and metabolic functions [9,10,11]. mTORC1 regulates protein production and cell metabolism, directly phosphorylating ribosomal S6 kinase (S6K) and promoting protein synthesis; S6K controls the translation of several mRNAs that encode many protein components [12,13,14,15]
PD-L1 expression was significantly increased in primary tumour tissues compared with adjacent normal tissues (ANT) (Figure 1A), supporting the potential relationship between ovarian carcinoma proliferation and PD-L1 expression
Summary
Ovarian cancer (OC) is one of the most common malignant tumours in women, and its mortality rate ranks first among gynaecological tumours [1,2]. The means of inhibiting tumour proliferation and increasing the survival rate are not completely clear. The PI3K–AKT signalling pathway is crucial for regulating many cellular functions, which it does by modulating the phosphorylation, transcription and translation of the downstream targets necessary for catabolic and anabolic processes [4,5,6,7,8]. Preclinical studies demonstrated that AKT is activated frequently in OC, resulting in over-activation of AKT signalling cascades, including migration or invasion, proliferation, apoptosis, survival and metabolic functions [9,10,11]. MTORC1 regulates protein production and cell metabolism, directly phosphorylating ribosomal S6 kinase (S6K) and promoting protein synthesis; S6K controls the translation of several mRNAs that encode many protein components [12,13,14,15]. Phosphorylation of S6K1 (P-S6K1) is a key biomarker of functional mTOR pathway activation and is abnormally expressed in prostate cancer, melanoma, breast cancer, lung cancer and colorectal cancer [16,17,18,19]
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