Secretogranin II impairs tumor growth and angiogenesis by promoting degradation of hypoxia‐inducible factor‐1α in colorectal cancer

Distant metastasis is a major cause of death in patients with colorectal cancer (CRC) but the management of advanced and metastatic CRC still remains problematic due to the distinct molecular alterations during tumor progression. Tumor angiogenesis is a key step in tumor growth, invasion and metasta...

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Autores principales:	Chao Fang, Lei Dai, Cun Wang, Chuanwen Fan, Yongyang Yu, Lie Yang, Hongxin Deng, Zongguang Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	angiogenesis colorectal cancer hypoxia‐inducible factor secretogranin II vascular endothelial growth factor Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/16171c752eea496b94f6bfdb3858d1b5
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spelling	oai:doaj.org-article:16171c752eea496b94f6bfdb3858d1b52021-12-02T10:31:06ZSecretogranin II impairs tumor growth and angiogenesis by promoting degradation of hypoxia‐inducible factor‐1α in colorectal cancer1878-02611574-789110.1002/1878-0261.13044https://doaj.org/article/16171c752eea496b94f6bfdb3858d1b52021-12-01T00:00:00Zhttps://doi.org/10.1002/1878-0261.13044https://doaj.org/toc/1574-7891https://doaj.org/toc/1878-0261Distant metastasis is a major cause of death in patients with colorectal cancer (CRC) but the management of advanced and metastatic CRC still remains problematic due to the distinct molecular alterations during tumor progression. Tumor angiogenesis is a key step in tumor growth, invasion and metastasis. However, the signaling pathways involved in angiogenesis are poorly understood. The results of the present study showed that secretogranin II (SCG2) was significantly downregulated in malignant CRC tissues, and higher expression of SCG2 was correlated with longer disease‐free survival and overall survival of CRC patients. The results of an animal study showed that ectopic expression of SCG2 significantly inhibited CRC tumor growth by disrupting angiogenesis. Furthermore, the inhibition of expression of vascular endothelial growth factor (VEGF) by SCG2 and rescue of VEGF effectively blocked SCG2‐induced inhibition of angiogenesis. Investigations into the underlying mechanism suggested that SCG2 promoted degradation of hypoxia‐inducible factor (HIF)‐1α by interacting with the von Hippel–Lindau tumor suppressor in CRC cells. Blocking of degradation of HIF‐1α effectively attenuated the SCG2‐mediated decrease in expression of VEGF in CRC cells. Collectively, these results demonstrated that treatment with SCG2 effectively inhibited CRC tumor growth by disrupting the activities of HIF‐1α/VEGF, thereby clarifying the anti‐tumor and anti‐angiogenesis roles of SCG2 in CRC, while providing a novel therapeutic target and a potential prognostic marker of disease progression.Chao FangLei DaiCun WangChuanwen FanYongyang YuLie YangHongxin DengZongguang ZhouWileyarticleangiogenesiscolorectal cancerhypoxia‐inducible factorsecretogranin IIvascular endothelial growth factorNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Oncology, Vol 15, Iss 12, Pp 3513-3526 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	angiogenesis colorectal cancer hypoxia‐inducible factor secretogranin II vascular endothelial growth factor Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	angiogenesis colorectal cancer hypoxia‐inducible factor secretogranin II vascular endothelial growth factor Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Chao Fang Lei Dai Cun Wang Chuanwen Fan Yongyang Yu Lie Yang Hongxin Deng Zongguang Zhou Secretogranin II impairs tumor growth and angiogenesis by promoting degradation of hypoxia‐inducible factor‐1α in colorectal cancer
description	Distant metastasis is a major cause of death in patients with colorectal cancer (CRC) but the management of advanced and metastatic CRC still remains problematic due to the distinct molecular alterations during tumor progression. Tumor angiogenesis is a key step in tumor growth, invasion and metastasis. However, the signaling pathways involved in angiogenesis are poorly understood. The results of the present study showed that secretogranin II (SCG2) was significantly downregulated in malignant CRC tissues, and higher expression of SCG2 was correlated with longer disease‐free survival and overall survival of CRC patients. The results of an animal study showed that ectopic expression of SCG2 significantly inhibited CRC tumor growth by disrupting angiogenesis. Furthermore, the inhibition of expression of vascular endothelial growth factor (VEGF) by SCG2 and rescue of VEGF effectively blocked SCG2‐induced inhibition of angiogenesis. Investigations into the underlying mechanism suggested that SCG2 promoted degradation of hypoxia‐inducible factor (HIF)‐1α by interacting with the von Hippel–Lindau tumor suppressor in CRC cells. Blocking of degradation of HIF‐1α effectively attenuated the SCG2‐mediated decrease in expression of VEGF in CRC cells. Collectively, these results demonstrated that treatment with SCG2 effectively inhibited CRC tumor growth by disrupting the activities of HIF‐1α/VEGF, thereby clarifying the anti‐tumor and anti‐angiogenesis roles of SCG2 in CRC, while providing a novel therapeutic target and a potential prognostic marker of disease progression.
format	article
author	Chao Fang Lei Dai Cun Wang Chuanwen Fan Yongyang Yu Lie Yang Hongxin Deng Zongguang Zhou
author_facet	Chao Fang Lei Dai Cun Wang Chuanwen Fan Yongyang Yu Lie Yang Hongxin Deng Zongguang Zhou
author_sort	Chao Fang
title	Secretogranin II impairs tumor growth and angiogenesis by promoting degradation of hypoxia‐inducible factor‐1α in colorectal cancer
title_short	Secretogranin II impairs tumor growth and angiogenesis by promoting degradation of hypoxia‐inducible factor‐1α in colorectal cancer
title_full	Secretogranin II impairs tumor growth and angiogenesis by promoting degradation of hypoxia‐inducible factor‐1α in colorectal cancer
title_fullStr	Secretogranin II impairs tumor growth and angiogenesis by promoting degradation of hypoxia‐inducible factor‐1α in colorectal cancer
title_full_unstemmed	Secretogranin II impairs tumor growth and angiogenesis by promoting degradation of hypoxia‐inducible factor‐1α in colorectal cancer
title_sort	secretogranin ii impairs tumor growth and angiogenesis by promoting degradation of hypoxia‐inducible factor‐1α in colorectal cancer
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/16171c752eea496b94f6bfdb3858d1b5
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Secretogranin II impairs tumor growth and angiogenesis by promoting degradation of hypoxia‐inducible factor‐1α in colorectal cancer

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