From crypt stem cell to colorectal cancer

Transcription

1 Chinese Bulletin of Life Sciences Vol. 19, No. 3 Jun., (2007) ( ) Wnt Notch BMP R735.35; R A From crypt stem cell to colorectal cancer WEN Bin*, CHEN Weiwen (Guangzhou University of Chinese Medicine, Guangzhou , China) Abstract: The intestinal epithelium follows the paradigms of stem cell biology established for other self-renewing tissues. With a unique topology, it constitutes a two-dimensional structure folded into valleys and hills: the proliferative crypts and the differentiated villi. Its unprecedented self-renewal rate appears reflected in a high susceptibility to renewal and those that underlie colorectal cancer are remarkably symmetrical. Wnt BMP and Notch signaling cascades play a critical roles in epithelial self-renewal and cancer. The malignant transformation of the intestinal epithelial cells does not rely on mutational changes in generic oncogenes or tumor suppressors, rather, the transformation process appears to specifically subvert the physiological regulators of the epithelium, the mutation of colon stem cell maybe an initial story of oncogenesis, colorectal cancer is the results of depressed of colon stem cell differention. Key words: colorectal cancer; crypt stem cell; tumour stem cell; signaling transduction [1-2] [3] ( ) (1971 ) * wen_bin04@yahoo.com.cn

2 322 [1,4] [2-5] Glinsky [6] 10 (stem cell-like) [7] Sell Pierce [8] (first-hit) 4 7 [9] (second-hit) Trosko Chang [10] (tumor stem cell theory) 2 [4] - (transit-amplifying cell, TA Cells) (binary lineage decisions) [11] [12-13] - - (transit-amplifying cell, TA) TA (transitamplifying zone) (intestinal subepithelial myofibroblasts ISEMFs) [14] ISEMFs Wnt ISEMFs [15] [12] % 5% 1951 Jackman Mayo Dukes - (adenomacarcinoma sequence)

3 d - Campbell [16] (the bottom-up theory) Shih [17] ( the top-down theory) Preston [18] Campbell [19] Cairns 1975 (immortal strand) [20] ( )(original strand) TA DNA Cairns [4] 3.2 Wnt - (cell fate) (dominant force) [2-3,21] [21-22] Notch BMP [23-25] Wnt WNT 19 FZ 10 [26] Wnt FZ canonical β-catenin planar Ca 2+ [27] canonical Wnt E-cadherin β-catenin (destruction complex) β-catenin β- catenin Wnt β-catenin FZ β-catenin [26-27] β-catenin TCF4 MYC [28] van de Wetering [29] DNA TCF4/β-catenin [27] Dickkopf 1 (Dkk-1, Wnt ) [30]

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