ANGPTL4 T266M variant is associated with reduced cancer invasiveness
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 r...
| Main Authors: | , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
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2018
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| Online Access: | https://hdl.handle.net/10356/87230 http://hdl.handle.net/10220/44354 |
| _version_ | 1811677375088295936 |
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| author | 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 |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) 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 |
| author_sort | Tan, Zhen Wei |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T02:36:22Z |
| format | Journal Article |
| id | ntu-10356/87230 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:36:22Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/872302020-11-01T05:11:03Z ANGPTL4 T266M variant is associated with reduced cancer invasiveness 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 Lee Kong Chian School of Medicine (LKCMedicine) School of Biological Sciences Singapore Phenome Centre ANGPTL4 Anoikis resistance 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. MOE (Min. of Education, S’pore) Accepted version 2018-01-29T03:44:56Z 2019-12-06T16:37:44Z 2018-01-29T03:44:56Z 2019-12-06T16:37:44Z 2017 Journal Article Tan, Z. W., Teo, Z., Tan, C., Choo, C. C., Loo, W. S., Song, Y., et al. (2017). ANGPTL4 T266M variant is associated with reduced cancer invasiveness. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1864(10), 1525-1536. 0167-4889 https://hdl.handle.net/10356/87230 http://hdl.handle.net/10220/44354 10.1016/j.bbamcr.2017.06.010 en Biochimica et Biophysica Acta (BBA) - Molecular Cell Research © 2017 Elsevier. This is the author created version of a work that has been peer reviewed and accepted for publication by Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Elsevier. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1016/j.bbamcr.2017.06.010]. 34 p. application/pdf |
| spellingShingle | ANGPTL4 Anoikis resistance 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 ANGPTL4 T266M variant is associated with reduced cancer invasiveness |
| title | ANGPTL4 T266M variant is associated with reduced cancer invasiveness |
| title_full | ANGPTL4 T266M variant is associated with reduced cancer invasiveness |
| title_fullStr | ANGPTL4 T266M variant is associated with reduced cancer invasiveness |
| title_full_unstemmed | ANGPTL4 T266M variant is associated with reduced cancer invasiveness |
| title_short | ANGPTL4 T266M variant is associated with reduced cancer invasiveness |
| title_sort | angptl4 t266m variant is associated with reduced cancer invasiveness |
| topic | ANGPTL4 Anoikis resistance |
| url | https://hdl.handle.net/10356/87230 http://hdl.handle.net/10220/44354 |
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