Proteomics of Smad4 regulated transforming growth factor-beta signalling in colon cancer cells

被引：38

作者：

Ali, Naveid Ahmad ^{[1
]}

McKay, Matthew John ^{[1
]}

Molloy, Mark Paul ^{[1
,2
]}

机构：

[1] Macquarie Univ, Dept Chem & Biomol Sci, Sydney, NSW 2109, Australia

[2] Macquarie Univ, Australian Proteome Anal Facil, Sydney, NSW 2109, Australia

来源：

MOLECULAR BIOSYSTEMS | 2010年 / 6卷 / 11期

基金：

澳大利亚研究理事会; 英国医学研究理事会;

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; TGF-BETA; CARCINOMA CELLS; LUNG-CANCER; IN-VITRO; PROTEIN; EXPRESSION; RECEPTOR; PATHWAY; BINDING;

D O I：

10.1039/c0mb00016g

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

TGF-beta signalling can play a paradoxical cell type specific role in cancer progression. Smad4 is a key mediator of the TGF-beta pathway, and is mutated and/or deleted in many cancers. To investigate Smad4 regulated TGF-beta signalling in colon cancer we conducted an iTRAQ mass spectrometry quantitative screen using wild type SW480 (Smad4 negative) colon carcinoma cells and stably restored Smad4 positive SW480 cells. In cells possessing a restored canonical TGF-beta signalling pathway, 48 h TGF-beta stimulation induced the expression of 15 proteins and repressed 1 protein, while in Smad4 wild type cells, TGF-beta induced 7 proteins and repressed 2 proteins. The expression of several S100 protein family members (A2, A4, A10, and A11), transgelin-2 and AKAP12, amongst others, were shown to be regulated by TGF-beta in a Smad4 dependent manner. We observed that S100 A4 could be repressed by TGF-beta, independently of Smad4 expression, while other Smad4 independent TGF-beta responses were restricted to induction of ribosomes and cytoskeletal proteins. Our proteomic screen has identified new Smad4 dependent and independent TGF-beta responses in colon carcinoma cells.

引用

页码：2332 / 2338

页数：7

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