title: Inversed relationship between CD44 variant and c-Myc due to oxidative stress-induced canonical Wnt activation.
abstract: Cancer stem-like cells express high amount of CD44 variant8-10 which protects cancer cells from redox stress. We have demonstrated by immunohistochemical analysis and Western blotting, and reverse-transcription polymerase chain reaction, that CD44 variant8-10 and c-Myc tend to show the inversed expression manner in gastric cancer cells. That is attributable to the oxidative stress-induced canonical Wnt activation, and furthermore, the up-regulation of the downstream molecules, one of which is oncogenic c-Myc, is not easily to occur in CD44 variant-positive cancer cells. We have also found out that CD44v8-10 expression is associated with the turn-over of the c-Myc with the experiments using gastric cancer cell lines. This cannot be simply explained by the model of oxidative stress-induced Wnt activation. CD44v8-10-positive cancer cells are enriched at the invasive front. Tumor tissue at the invasive area is considered to be composed of heterogeneous cellular population; dormant cancer stem-like cells with CD44v8-10 (high)/ Fbw7 (high)/ c-Myc (low) and proliferative cancer stem-like cells with CD44v8-10 (high)/ Fbw7 (low)/ c-Myc (high).
authors: Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address: medical21go@yahoo.co.jp.
authors: Go J
authors: GJ
authors: Yoshida
authors: Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Hideyuki
authors: H
authors: Saya
mesh_terms: D045744:Cell Line, Tumor; D014644:Genetic Variation; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D051153:Wnt Proteins
keywords: CD44 variant; Cancer stem-like cell; Fbw7; Gastric cancer; Redox stress-induced Wnt signal; c-Myc