Circular dorsal ruffles disturb the growth factor-induced PI3K-AKT pathway in hepatocellular carcinoma Hep3B cells

• DOI: 10.1186/s12964-022-00911-6
• Publication Date: 2022-07-07T13:06:28Z
• Authors: Xiaowei Sun; Yujie Liu; Shuheng Zhou; Li Wang; Jinzi Wei; Rui Hua; Zhongyang Shen; Sei Yoshida
• Keywords: Carcinoma, Hepatocellular; QH573-671; Epidermal Growth Factor; AKT; Research; Liver Neoplasms; R; Apoptosis; PI3K; Hep3B; Cell Line; 3. Good health; Phosphatidylinositol 3-Kinases; Circular dorsal ruffles; Cell Line, Tumor; Medicine; Humans; Phosphatidylinositol 3-Kinase; Cytology; Proto-Oncogene Proteins c-akt

Abstract Background Circular dorsal ruffles (CDRs) are rounded membrane induced on the surfaces of cells stimulated by growth factors (GF). They can serve as signal platforms to activate AKT protein kinase. After GF stimulation, phosphatidylinositol 3-kinase (PI3K) generates (3,4,5)-triphosphate (PIP3) in plasma membrane. PIP3 accumulates inside CDRs, recruits into structures, and phosphorylates them (pAKT). Given importance PI3K-AKT pathway signaling, CDRs likely involved cell growth. Interestingly, some cancer lines express CDRs. We hypothesized that contribute carcinogenesis modulating pathway. In present study, we identified CDR-expressing investigated their cellular functions. Methods CDR formation was examined six response epidermal factor (EGF) insulin. The morphology characterized, related signaling molecules were observed using confocal scanning electron microscopy. role studied biochemical analysis. actin inhibitor cytochalasin D (Cyto D) PI3K TGX221 used block Results treatment hepatocellular carcinoma (HCC) Hep3B line, but not others, including HCC HepG2 Huh7, LO2 hepatocyte line. Confocal microscopy western blot analysis showed PI3K-PIP3-AKT activated at receptor proteins recruited structures. Cyto completely blocked partially attenuated GF-induced pAKT. These results indicate regulate receptor-mediated existence CDR-independent pAKT mechanisms. Conclusions Our modulate cells. Since other lines, propose would determine characteristic aberrantly triggering Signaling promising therapeutic targets for types HCC.