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Updated: Feb 27, 2026
Author Spotlight: Advancing the Detection of Low-Frequency Mutations in Cancer Tissues
Published on: August 23, 2024
ANGPTL4 T266M variant is associated with reduced cancer invasiveness
Zhen Wei Tan1, Ziqiang Teo1, Carol Tan1
1School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
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.
Insights
The T266M mutation in C-terminal Angiopoietin-like 4 (cANGPTL4) impairs tumor cell binding to integrin α5β1, affecting cancer progression and energy metabolism.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Angiopoietin-like 4 (ANGPTL4) is a secretory protein implicated in cancer and metabolic processes.
- Point mutations in the C-terminal ANGPTL4 (cANGPTL4) have been identified but their functional significance remains unclear.
Purpose of the Study:
- To investigate the functional impact of the T266M mutation in cANGPTL4 on tumor characteristics and cellular processes.
- To compare tumors with wild-type (wt) cANGPTL4 and T266M cANGPTL4.
Main Methods:
- Comparative analysis of tumor characteristics with wt cANGPTL4 and T266M cANGPTL4.
- Assessment of T266M cANGPTL4 binding affinity to integrin α5β1.
- Evaluation of downstream signaling, tumor cell proliferation, anoikis resistance, migration, and energy metabolism.
Main Results:
- T266M cANGPTL4 exhibited reduced binding affinity to integrin α5β1 compared to wt cANGPTL4.
- Mutant tumors showed impaired proliferation, anoikis resistance, and migratory capability.
- Reduced adenylate energy charge and altered Glut2 expression were observed in tumors with T266M cANGPTL4.
Conclusions:
- The T266M mutation in cANGPTL4 affects integrin binding, leading to significant alterations in tumor cell behavior and energy metabolism.
- These findings provide insights into the role of cANGPTL4 mutations in cancer progression and metabolic dysregulation.
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