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(Journal Article) |
Biochimica et biophysica acta 1864 (10): 1525-1536 (2017)
ANGPTL4 T266M variant is associated with reduced cancer invasiveness.
Zhen Wei Tan
,
Ziqiang Teo
,
Carol Tan
,
Chee Chong Choo
,
Wei Sheng Loo
,
Yiyang Song
,
Zhi Yang Tam
,
Sean Pin Ng
,
Hong Zheng Koh
,
Yi Siang Ng
,
Susana Geifman Shochat
,
Yin Hoe Yau
,
Pengcheng Zhu
,
Nguan Soon Tan
ABSTRACT
Angiopoietin-like 4 (ANGPTL4) is a secretory protein that can be cleaved to form an N-terminal and a C-terminal protein. Studies performed thus far have linked ANGPTL4 to several cancer-related and metabolic processes. Notably, several point mutations in the C-terminal ANGPTL4 (cANGPTL4) have been reported, although no studies have been performed that ascribed these mutations to cancer-related and metabolic processes. In this study, we compared the characteristics of tumors with and without wild-type (wt) cANGPTL4 and tumors with cANGPTL4 bearing the T266M mutation (T266M cANGPTL4). We found that T266M cANGPTL4 bound to integrin α5β1 with a reduced affinity compared to wt, leading to weaker activation of downstream signaling molecules. The mutant tumors exhibited impaired proliferation, anoikis resistance, and migratory capability and had reduced adenylate energy charge. Further investigations also revealed that cANGPTL4 regulated the expression of Glut2. These findings may explain the differences in the tumor characteristics and energy metabolism observed with the cANGPTL4 T266M mutation compared to tumors without the mutation.