Journal
FRONTIERS IN ONCOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.655302
Keywords
CD155; cervical cancer; carcinogenesis; AKT/mTOR; NF-kappa B
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Funding
- National Natural Science Foundation of China (NSFC) [81902644]
- Shandong Provincial Natural Science Foundation, China [ZR2019BC059, ZR2020QH248]
- Science and Technology Development Project of Shandong Province [2019GSF108126]
- Key Research Project of Shandong Province [2017CXGC1210]
- Weifang Health Fund [2018-053]
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The study found that the expression of CD155 gradually increases in cervical cancer, reducing CD155 expression can inhibit cell proliferation and tumor formation, while CD155 overexpression has the opposite effect. Interaction between CD155 and AKT forms a complex, activating the AKT/mTOR/NF-κB pathway and inhibiting autophagy and apoptosis.
Expression of the immunoglobulin superfamily member CD155 was increased in a variety of human malignancies, but the role of CD155 in tumorigenesis and tumor development in cervical cancer has not been elucidated. In this study, immunohistochemistry and enzyme-linked immunosorbent assay analyses showed that CD155 expression gradually increases with the degree of cervical lesions. In vitro and in vivo, reducing the expression of CD155 inhibited cell proliferation, cell viability and tumor formation and arrested the cell cycle in G0/G1 phase. Antibody array-based profiling of protein phosphorylation revealed that CD155 knockdown can inhibited the AKT/mTOR/NF-kappa B pathway and activated autophagy and apoptosis; the opposite effects were observed upon CD155 has overexpression. We proved that there is an interaction between CD155 and AKT by immunoprecipitation. We further confirmed the mechanism between CD155 and AKT/mTOR/NF-kappa B through rescue experiments. AKT knockdown reversed the antiapoptotic effects and activation of the AKT/mTOR/NF-kappa B pathway induced by CD155 overexpression. Our research demonstrated that CD155 can interact with AKT to form a complex, activates the AKT/mTOR/NF-kappa B pathway and inhibit autophagy and apoptosis. Thus, CD155 is a potential screening and therapeutic biomarker for cervical cancer.
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