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Angiopoietin-like 4 protein elevates the prosurvival intracellular O2(-) : H2O2 ratio and confers anoikis resistance to tumors

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Angiopoietin-like 4 protein elevates the prosurvival intracellular O2(-) : H2O2 ratio and confers anoikis resistance to tumors

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Title: Angiopoietin-like 4 protein elevates the prosurvival intracellular O2(-) : H2O2 ratio and confers anoikis resistance to tumors
Author: Zhu, Pengcheng; Tan, Ming Jie; Huang, Royston-Luke; Tan, Chek Kun; Chong, Han Chung; Pal, Mintu; Lam, Ivan Chee Ren; Boukamp, Petra; Pan, Jiun Yit; Tan, Suat Hoon; Kersten, Sander; Li, Hoi-Yeung; Ding, Jeak Ling; Tan, Nguan Soon
Copyright year: 2011
Abstract: Cancer is a leading cause of death worldwide. Tumor cells exploit various signaling pathways to promote their growth and metastasis. To our knowledge, the role of angiopoietin-like 4 protein (ANGPTL4) in cancer remains undefined. Here, we found that elevated ANGPTL4 expression is widespread in tumors, and its suppression impairs tumor growth associated with enhanced apoptosis. Tumor-derived ANGPTL4 interacts with integrins to stimulate NADPH oxidase-dependent production of O2(-). A high ratio of O2:(-)H2O2 oxidizes/activates Src, triggering the PI3K/PKBα and ERK prosurvival pathways to confer anoikis resistance, thus promoting tumor growth. ANGPTL4 deficiency results in diminished O2(-) production and a reduced O2:(-)H2O2 ratio, creating a cellular environment conducive to apoptosis. ANGPTL4 is an important redox player in cancer and a potential therapeutic target.
Subject: DRNTU::Science::Biological sciences::Cytology.
Type: Journal Article
Series/ Journal Title: Cancer cell
School: School of Biological Sciences
Rights: © 2011 Elsevier Inc. This is the author created version of a work that has been peer reviewed and accepted for publication by Cancer Cell, Elsevier. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [DOI: http://dx.doi.org/10.1016/j.ccr.2011.01.018 ]

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