Kim, Somi Cho, Chang Yun Lee, Doohyung Song, Dae-Geun Kim, Hye-Jin Jung, Jae Woo Kim, Ji Eon Park, Dasomi Lee, Haesong Um, Hyejin Park, Jinsoo Choi, Yoonjeong Kim, Yoomin Nam, Seo Hee Lee, Jung Weon 2024-01-19T21:30:25Z 2024-01-19T21:30:25Z 2021-09-03 2018-12 0304-3835 https://pubs.kist.re.kr/handle/201004/120655 CD133 is a surface marker of liver cancer stem cells. Transmembrane 4 L six family member 5 (TM4SF5) promotes sphere growth and circulation. However, it is unknown how CD133 and TM4SF5 cross-talk with each other for cancer stem cell properties. Here, we investigated the significance of inter-relationships between CD133, TM4SF5, CD44, and protein tyrosine phosphatase receptor type F (PTPRF) in a three-dimensional (3D) sphere growth system. We found that CD133 upregulated TM4SF5 and CD44, whereas TM4SF5 and CD44 did not affect CD133 expression. Signaling activity following CD133 phosphorylation caused TM4SF5 expression and sphere growth. TM4SF5 bound to CD133 and promoted c-Src activity for CD133 phosphorylation as a positive feedback loop, leading to CD133-mediated sphere growth that was inhibited by TM4SF5 inhibition or suppression. TM4SF5 also bound PTPRF and promoted paxillin phosphorylation. Decreased sphere growth upon CD133 suppression was recovered by TM4SF5 expression and partially by PTPRF suppression. TM4SF5 inhibition enhanced PTPRF levels and abolished PTPRF suppression-mediated sphere growth. Altogether, CD133-induced TM4SF5 expression and function were important for liver cancer sphere growth and may be a promising target to block metastasis. English ELSEVIER IRELAND LTD CANCER STEM-CELLS EPITHELIAL-MESENCHYMAL TRANSITION HEPATOCELLULAR-CARCINOMA LIVER-CANCER STEM/PROGENITOR CELLS SELF-RENEWAL COLON-CANCER INHIBITION EGFR GLYCOGEN-SYNTHASE-KINASE-3-BETA CD133-induced TM4SF5 expression promotes sphere growth via recruitment and blocking of protein tyrosine phosphatase receptor type F (PTPRF) Article 10.1016/j.canlet.2018.09.009 1 CANCER LETTERS, v.438, pp.219 - 231 CANCER LETTERS 438 219 231 scie scopus 000449139400022 2-s2.0-85053836896 Oncology Oncology Article CANCER STEM-CELLS EPITHELIAL-MESENCHYMAL TRANSITION HEPATOCELLULAR-CARCINOMA LIVER-CANCER STEM/PROGENITOR CELLS SELF-RENEWAL COLON-CANCER INHIBITION EGFR GLYCOGEN-SYNTHASE-KINASE-3-BETA 3D hepatic sphere Membrane protein markers Proliferation Protein interaction Signal transduction