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Title: Angiopoietin-like 4 Protein Elevates the Prosurvival Intracellular O2-:H2O2 Ratio and Confers Anoikis Resistance to Tumors
Authors: Zhu, P.
Tan, M.
Huang, R.-L.
Tan, C.
Chong, H.
Pal, M.
Lam, C.
Boukamp, P.
Pan, J.
Tan, S.
Kersten, S.
Li, H.
Ding, J. 
Tan, N.
Issue Date: 8-Mar-2011
Citation: Zhu, P., Tan, M., Huang, R.-L., Tan, C., Chong, H., Pal, M., Lam, C., Boukamp, P., Pan, J., Tan, S., Kersten, S., Li, H., Ding, J., Tan, N. (2011-03-08). Angiopoietin-like 4 Protein Elevates the Prosurvival Intracellular O2-:H2O2 Ratio and Confers Anoikis Resistance to Tumors. Cancer Cell 19 (3) : 401-415. ScholarBank@NUS Repository.
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 O 2 -. A high ratio of O 2 -:H 2O 2 oxidizes/activates Src, triggering the PI3K/PKBα and ERK prosurvival pathways to confer anoikis resistance, thus promoting tumor growth. ANGPTL4 deficiency results in diminished O 2 - production and a reduced O 2 -:H 2O 2 ratio, creating a cellular environment conducive to apoptosis. ANGPTL4 is an important redox player in cancer and a potential therapeutic target. © 2011 Elsevier Inc.
Source Title: Cancer Cell
ISSN: 15356108
DOI: 10.1016/j.ccr.2011.01.018
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