Polarity switching of ovarian cancer cell clusters via SRC family kinase is involved in the peritoneal dissemination

• DOI: 10.1111/cas.15493
• Publication Date: 2022-07-18T13:30:12Z
• Authors: Mayuko Kawata; Jumpei Kondo; Kunishige Onuma; Yu Ito; Takeshi Yokoi; Junzo Hamanishi; Masaki Mandai; Tadashi Kimura; Masahiro Inoue
• Keywords: Organoid; Src family kinase; Cell polarity

Peritoneal dissemination is a predominant pattern of metastasis in patients with advanced ovarian cancer. Despite recent progress the management strategy, peritoneal remains determinant poor cancer prognosis. Using various histological types patient-derived organoids, roles apicobasal polarity cell clusters were studied. First, it was found that both tissues and organoids showed polarity, where zonula occludens-1 (ZO-1) integrin beta 4 (ITGB4) served as markers for apical basal sides, respectively. The suspension culture, model cluster floating ascites, apical-out/basal-in status, while once embedded extracellular matrix (ECM), switched their to apical-in/basal-out. This switch accompanied by SRC kinase family (SFK) phosphorylation inhibited SFK inhibitors. inhibitors abrogated adherence onto ECM-coated plastic surface. When seeded on mesothelial layer, they cleared invaded cells. In vivo, dasatinib, an inhibitor, suppressed immunodeficient mice. These results suggest SFK-mediated switching involved metastasis. Polarity would be potential therapeutic target suppressing