Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Biochem Biophys Res Commun. 2014 Jan 10;443(2):622-7. doi: 10.1016/j.bbrc.2013.12.016. Epub 2013 Dec 11.
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).
肿瘤干细胞样细胞表达高水平的 CD44 变体 8-10，这可以保护癌细胞免受氧化应激。我们通过免疫组织化学分析、Western blot 和逆转录聚合酶链反应证实，CD44 变体 8-10 和 c-Myc 在胃癌细胞中呈现相反的表达模式。这归因于氧化应激诱导的经典 Wnt 激活，此外，下游分子的上调，其中一个是致癌的 c-Myc，在 CD44 变体阳性的癌细胞中不容易发生。我们还发现，CD44v8-10 的表达与胃癌细胞系中 c-Myc 的周转有关。这不能简单地用氧化应激诱导的 Wnt 激活模型来解释。CD44v8-10 阳性的癌细胞富集在侵袭前沿。侵袭区域的肿瘤组织被认为是由异质细胞群组成的；具有 CD44v8-10（高）/Fbw7（高）/c-Myc（低）的休眠肿瘤干细胞样细胞和具有 CD44v8-10（高）/Fbw7（低）/c-Myc（高）的增殖肿瘤干细胞样细胞。
