Author/Authors :
Zhu، نويسنده , , Pengcheng and Tan، نويسنده , , Ming Jie and Huang، نويسنده , , Royston-Luke and Tan، نويسنده , , Chek Kun and Chong، نويسنده , , Han Chung and Pal، نويسنده , , Mintu and Lam، نويسنده , , Chee Ren Ivan and Boukamp، نويسنده , , Petra and Pan، نويسنده , , Jiun Yit and Tan، نويسنده , , Suat Hoon and Kersten، نويسنده , , Sander and Li، نويسنده , , Hoi Yeung and Ding، نويسنده , , Jeak Ling and Tan، نويسنده , , Nguan Soon Tan، نويسنده ,
Abstract :
Summary
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.
