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WWOX Regulation of Cancer Stem Cell Sphere Formation
Author(s) -
Chen YuAn,
Chou PeiYi,
Chen HsinFu,
Chang NanShan
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.629.1
Subject(s) - wwox , cancer research , cancer , stem cell , cancer stem cell , cell , medicine , microbiology and biotechnology , biology , genetics , suppressor
Time‐lapse microscopy revealed that triple negative and WWOX negative breast cancer MDA‐MB‐231 cells are highly aggressive. They sense the surrounding WWOX‐expressing normal or cancer cells, run away from them, and divide rapidly in order to survive. With time of growth and increased space pressure, breast cancer stem cells grow as spheres with the expression of pluripotent stem cell markers such as Oct4, SSEA‐4, TRA‐1‐60, and others. WWOX is re‐expressed in the cancer stem cell spheres with S14 phosphorylation (pS14). However pS14 disappears upon release of cells from the spheres. Notably, organs and organ cells, expressing pS14WWOX, are susceptible for cancer cell docking and homing both in vitro and in vivo . A synthetic peptide WWgre, surrounding the S14 area (but without S14 phosphorylation), effectively abolishes the growth of cancer xenografts in nude mice (100% suppression of breast and other cancer) for their entire lifetime, suggesting WWgre eradicates breast cancer stem cells. Scrambled peptides had no blocking effects against breast cancer growth. Together, WWOX plays a critical in controlling the proliferation and differentiation of cancer stem cells. (Supported in part by DoD, USA and MOST and NHRI, Taiwan)