Role of angiopoietin-like 4 in tumor growth.

Cancer is a leading cause of death worldwide. Tumor cells exploit various signaling molecules to promote their growth and metastasis. The angiopoietin-like 4 protein (ANGPTL4) has well-studied roles in metabolism, yet its role in cancer biology remains undefined. Herein, by using human tumor tissue...

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Main Author: Zhu, Pengcheng.
Other Authors: Tan Nguan Soon
Format: Theses and Dissertations
Language:English
Published: 2011
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Online Access:https://hdl.handle.net/10356/46431
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-464312023-02-28T18:50:55Z Role of angiopoietin-like 4 in tumor growth. Zhu, Pengcheng. Tan Nguan Soon School of Biological Sciences DRNTU::Science Cancer is a leading cause of death worldwide. Tumor cells exploit various signaling molecules to promote their growth and metastasis. The angiopoietin-like 4 protein (ANGPTL4) has well-studied roles in metabolism, yet its role in cancer biology remains undefined. Herein, by using human tumor tissue arrays, tumor cell lines and human skin tumor samples, we found that elevated ANGPTL4 expression is widespread in most known tumor types. Treating cancer cells with ANGPTl4-targeted RNAi or monoclonal antibodies imparts a significant decrease in in vivo tumor growth and induces apoptosis in cancer cell lines upon anoikis challenge. Mechanistic investigation suggests that tumor-derived ANGPTL4 interacts with integrins to stimulate the NADPH oxidase-dependent production of O2-. A high ratio of O2-:H2O2 oxidizes/activates Src, triggering the PI3K/PKBα and ERK pro-survival 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. In all, we show that enhanced expression of ANGPTL4 is common in tumors, and tumor-derived ANGPTL4 activates integrin-related, oxidant-dependent survival pathways, despite the loss of matrix attachment, suggesting ANGPTL4 as an important novel player in redox-mediated cancer progression. Our findings suggest that anticancer strategies focusing on redox-based apoptosis induction in tumors are viable. DOCTOR OF PHILOSOPHY (SBS) 2011-12-06T02:21:43Z 2011-12-06T02:21:43Z 2011 2011 Thesis Zhu, P. C. (2011). Role of angiopoietin-like 4 in tumor growth. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/46431 10.32657/10356/46431 en 292 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science
spellingShingle DRNTU::Science
Zhu, Pengcheng.
Role of angiopoietin-like 4 in tumor growth.
description Cancer is a leading cause of death worldwide. Tumor cells exploit various signaling molecules to promote their growth and metastasis. The angiopoietin-like 4 protein (ANGPTL4) has well-studied roles in metabolism, yet its role in cancer biology remains undefined. Herein, by using human tumor tissue arrays, tumor cell lines and human skin tumor samples, we found that elevated ANGPTL4 expression is widespread in most known tumor types. Treating cancer cells with ANGPTl4-targeted RNAi or monoclonal antibodies imparts a significant decrease in in vivo tumor growth and induces apoptosis in cancer cell lines upon anoikis challenge. Mechanistic investigation suggests that tumor-derived ANGPTL4 interacts with integrins to stimulate the NADPH oxidase-dependent production of O2-. A high ratio of O2-:H2O2 oxidizes/activates Src, triggering the PI3K/PKBα and ERK pro-survival 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. In all, we show that enhanced expression of ANGPTL4 is common in tumors, and tumor-derived ANGPTL4 activates integrin-related, oxidant-dependent survival pathways, despite the loss of matrix attachment, suggesting ANGPTL4 as an important novel player in redox-mediated cancer progression. Our findings suggest that anticancer strategies focusing on redox-based apoptosis induction in tumors are viable.
author2 Tan Nguan Soon
author_facet Tan Nguan Soon
Zhu, Pengcheng.
format Theses and Dissertations
author Zhu, Pengcheng.
author_sort Zhu, Pengcheng.
title Role of angiopoietin-like 4 in tumor growth.
title_short Role of angiopoietin-like 4 in tumor growth.
title_full Role of angiopoietin-like 4 in tumor growth.
title_fullStr Role of angiopoietin-like 4 in tumor growth.
title_full_unstemmed Role of angiopoietin-like 4 in tumor growth.
title_sort role of angiopoietin-like 4 in tumor growth.
publishDate 2011
url https://hdl.handle.net/10356/46431
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