Angiopoietin-like 4 Protein Elevates the Prosurvival Intracellular O2-:H2O2 Ratio and Confers Anoikis Resistance to Tumors

Pengcheng Zhu; Ming Jie Tan; Royston Luke Huang; Chek Kun Tan; Han Chung Chong; Mintu Pal; Chee Ren Ivan Lam; Petra Boukamp; Jiun Yit Pan; Suat Hoon Tan; Sander Kersten; Hoi Yeung Li; Jeak Ling Ding; Nguan Soon Tan

doi:10.1016/j.ccr.2011.01.018

Angiopoietin-like 4 Protein Elevates the Prosurvival Intracellular O2-:H2O2 Ratio and Confers Anoikis Resistance to Tumors

Pengcheng Zhu, Ming Jie Tan, Royston Luke Huang, Chek Kun Tan, Han Chung Chong, Mintu Pal, Chee Ren Ivan Lam, Petra Boukamp, Jiun Yit Pan, Suat Hoon Tan, Sander Kersten, Hoi Yeung Li, Jeak Ling Ding, Nguan Soon Tan^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

231 Citations (Scopus)

Abstract

Cancer is a leading cause of death worldwide. Tumor cells exploit various signaling pathways to promote their growth and metastasis. To our knowledge, the role of angiopoietin-like 4 protein (ANGPTL4) in cancer remains undefined. Here, we found that elevated ANGPTL4 expression is widespread in tumors, and its suppression impairs tumor growth associated with enhanced apoptosis. Tumor-derived ANGPTL4 interacts with integrins to stimulate NADPH oxidase-dependent production of O₂^-. A high ratio of O₂^-:H₂O₂ oxidizes/activates Src, triggering the PI3K/PKBα and ERK prosurvival 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. ANGPTL4 is an important redox player in cancer and a potential therapeutic target.

Original language	English
Pages (from-to)	401-415
Number of pages	15
Journal	Cancer Cell
Volume	19
Issue number	3
DOIs	https://doi.org/10.1016/j.ccr.2011.01.018
Publication status	Published - Mar 8 2011
Externally published	Yes

ASJC Scopus Subject Areas

Oncology
Cell Biology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ccr.2011.01.018

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Zhu, P., Tan, M. J., Huang, R. L., Tan, C. K., Chong, H. C., Pal, M., Lam, C. R. I., Boukamp, P., Pan, J. Y., Tan, S. H., Kersten, S., Li, H. Y., Ding, J. L., & Tan, N. S. (2011). Angiopoietin-like 4 Protein Elevates the Prosurvival Intracellular O2-:H2O2 Ratio and Confers Anoikis Resistance to Tumors. Cancer Cell, 19(3), 401-415. https://doi.org/10.1016/j.ccr.2011.01.018

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abstract = "Cancer is a leading cause of death worldwide. Tumor cells exploit various signaling pathways to promote their growth and metastasis. To our knowledge, the role of angiopoietin-like 4 protein (ANGPTL4) in cancer remains undefined. Here, we found that elevated ANGPTL4 expression is widespread in tumors, and its suppression impairs tumor growth associated with enhanced apoptosis. Tumor-derived ANGPTL4 interacts with integrins to stimulate NADPH oxidase-dependent production of O2-. A high ratio of O2-:H2O2 oxidizes/activates Src, triggering the PI3K/PKBα and ERK prosurvival 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. ANGPTL4 is an important redox player in cancer and a potential therapeutic target.",

author = "Pengcheng Zhu and Tan, {Ming Jie} and Huang, {Royston Luke} and Tan, {Chek Kun} and Chong, {Han Chung} and Mintu Pal and Lam, {Chee Ren Ivan} and Petra Boukamp and Pan, {Jiun Yit} and Tan, {Suat Hoon} and Sander Kersten and Li, {Hoi Yeung} and Ding, {Jeak Ling} and Tan, {Nguan Soon}",

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AU - Huang, Royston Luke

AU - Tan, Chek Kun

AU - Chong, Han Chung

AU - Pal, Mintu

AU - Lam, Chee Ren Ivan

AU - Boukamp, Petra

AU - Pan, Jiun Yit

AU - Tan, Suat Hoon

AU - Kersten, Sander

AU - Li, Hoi Yeung

AU - Ding, Jeak Ling

AU - Tan, Nguan Soon

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N2 - Cancer is a leading cause of death worldwide. Tumor cells exploit various signaling pathways to promote their growth and metastasis. To our knowledge, the role of angiopoietin-like 4 protein (ANGPTL4) in cancer remains undefined. Here, we found that elevated ANGPTL4 expression is widespread in tumors, and its suppression impairs tumor growth associated with enhanced apoptosis. Tumor-derived ANGPTL4 interacts with integrins to stimulate NADPH oxidase-dependent production of O2-. A high ratio of O2-:H2O2 oxidizes/activates Src, triggering the PI3K/PKBα and ERK prosurvival 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. ANGPTL4 is an important redox player in cancer and a potential therapeutic target.

AB - Cancer is a leading cause of death worldwide. Tumor cells exploit various signaling pathways to promote their growth and metastasis. To our knowledge, the role of angiopoietin-like 4 protein (ANGPTL4) in cancer remains undefined. Here, we found that elevated ANGPTL4 expression is widespread in tumors, and its suppression impairs tumor growth associated with enhanced apoptosis. Tumor-derived ANGPTL4 interacts with integrins to stimulate NADPH oxidase-dependent production of O2-. A high ratio of O2-:H2O2 oxidizes/activates Src, triggering the PI3K/PKBα and ERK prosurvival 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. ANGPTL4 is an important redox player in cancer and a potential therapeutic target.

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Angiopoietin-like 4 Protein Elevates the Prosurvival Intracellular O2-:H2O2 Ratio and Confers Anoikis Resistance to Tumors

Abstract

ASJC Scopus Subject Areas

UN SDGs

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