CD133-induced TM4SF5 expression promotes sphere growth via recruitment and blocking of protein tyrosine phosphatase receptor type F (PTPRF). (1st December 2018)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Cancer letters. Volume 438(2018)
• Page Start: 219
• Page End: 231
• Publication Date: 2018-12-01
• Subjects: 3D hepatic sphere -- Membrane protein markers -- Proliferation -- Protein interaction -- Signal transduction; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2018.09.009
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: 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. Highlights: The role of TM4SF5 and CD133 cross-talk in the CSC properties of HCC is unknown. CD133-induced c-Src, Akt, and β-catenin signaling mediates TM4SF5 induction. TM4SF5 drives CD133 phosphorylation via a bidirectional positive feedback loop. TM4SF5 binds PTPRF to regulate cellular signaling for anchorage-independent growth. CD133/TM4SF5/PTPRF and CD44 are potential biomarkers for HCC metastasis.