ANGPTL4 T266M variant is associated with reduced cancer invasiveness

作者：Tan Zhen Wei; Teo Ziqiang; Tan Carol; Choo Chee Chong; Loo Wei Sheng; Song Yiyang; Tam Zhi Yang; Ng Sean Pin; Koh Hong Zheng; Ng Yi Siang; Shochat Susana Geifman; Yau Yin Hoe; Zhu Pengcheng; Tan Nguan Soon

来源：Biochimica et Biophysica Acta-Molecular Cell Research, 2017, 1864(10): 1525-1536.

DOI：10.1016/j.bbamcr.2017.06.010

• ANGPTL4
• Anoikis resistance
• Invasiveness
• Tumor growth
• Cell metabolism
• MALDI imaging

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 alpha 5 beta 1 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.

• 出版日期2017-10
• 单位南阳理工学院