DHX32 Promotes Angiogenesis in Colorectal Cancer Through Augmenting β-catenin Signaling to Induce Expression of VEGFA

Autor: Zhongying Zhang, Chao Pan, Peihua Li, Hongfeng Liao, Zhiyuan Lin, Chunlei Ye, Qing Hu, Huayue Lin, Yizhen Fang, Jingkun Wang, Zanxi Fang, Qing Luo, Yuanhui Su, Fen Wang
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Male
Vascular Endothelial Growth Factor A
0301 basic medicine
Pathology
Angiogenesis
Colorectal cancer
lcsh:Medicine
Metastasis
DEAD-box RNA Helicases
Mice
Transcription (biology)
Wnt Signaling Pathway
Microvessel
beta Catenin
Mice
Inbred BALB C
lcsh:R5-920
Neovascularization
Pathologic
General Medicine
Middle Aged
Gene Expression Regulation
Neoplastic
Vascular endothelial growth factor A
Female
β catenin signaling
Colorectal Neoplasms
TCF Transcription Factors
lcsh:Medicine (General)
Research Paper
Signal Transduction
VEGFA
medicine.medical_specialty
DHX32
Mice
Nude
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Downregulation and upregulation
Cell Line
Tumor
Human Umbilical Vein Endothelial Cells
medicine
Animals
Humans
Cell Proliferation
business.industry
lcsh:R
β-catenin
HCT116 Cells
medicine.disease
digestive system diseases
030104 developmental biology
Cancer research
business
Zdroj: EBioMedicine, Vol 18, Iss C, Pp 62-72 (2017)
EBioMedicine
ISSN: 2352-3964
Popis: We previously reported that overexpression of DHX32 contributes to the growth and metastasis of colorectal cancer (CRC). However, the underlying mechanism is not largely characterized. Herein, we reported that DHX32 in CRC cells upregulated expression of vascular endothelial growth factor A (VEGFA) at the transcription level through interacting with and stabilizing β-catenin. This promoted the recruitment of host endothelial cells to the tumor, and therefore, formation of microvessel in the tumor. Xenograft model revealed that depletion of DHX32 in CRC cells significantly reduced the microvessel density in the grafts and suppressed the growth of grafts. Furthermore, the expression level of DHX32 was positively associated with microvessel density in human CRC and poor outcome of CRC patients. Therefore, the report demonstrates that DHX32 is a pro-angiogenic factor, that inhibition of DHX32-β-catenin pathway can provide a strategy for CRC treatment, and that the expression level of DHX32 has the potential to serve as a biomarker for CRC diagnosis and prognosis.
Highlights • DHX32 upregulates VEGFA expression through interacting with and stabilizing β-catenin. • DHX32 promotes colorectal cancer cells to recruit endothelial cells and induces angiogenesis. • DHX32 is associated with tumor angiogenesis and poor prognosis of colorectal cancer patients. Tumor angiogenesis is required for cancer growth and metastasis. Understanding the molecular mechanism by which cancer cells promote angiogenesis is required to develop effective cancer treatment. In this study, we reported that DHX32 is a pro-angiogenic factor in colorectal cancer. Aberrantly expressed DHX32 promoted tumor angiogenesis by stabilizing β-catenin and increasing the expression of vascular endothelial growth factor. The results suggested that suppression of DHX32 can be of therapeutic value for colorectal cancer and that expression level of DHX32 has the potential to serve as a biomarker for colorectal cancer diagnosis and prognosis.
Databáze: OpenAIRE
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