[PDF][PDF] Angiopoietin-like 4 protein elevates the prosurvival intracellular O2−: H2O2 ratio and confers anoikis resistance to tumors
Cancer cell, 2011•cell.com
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 2 O 2 …
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 2 O 2 …
Summary
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.
cell.com