DHX32 Promotes Angiogenesis in Colorectal Cancer Through Augmenting β-catenin Signaling to Induce Expression of VEGFA.
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.
Center for Clinical Laboratory, Xiamen University Affiliated Zhongshan Hospital, Xiamen, China.
Huayue
H
Lin
Center for Clinical Laboratory, Xiamen University Affiliated Zhongshan Hospital, Xiamen, China.
Zanxi
Z
Fang
Center for Clinical Laboratory, Xiamen University Affiliated Zhongshan Hospital, Xiamen, China.
Yuanhui
Y
Su
Center for Clinical Laboratory, Xiamen University Affiliated Zhongshan Hospital, Xiamen, China.
Peihua
P
Li
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.
Jingkun
J
Wang
Department of Pathology, Xiamen University Affiliated Zhongshan Hospital, Xiamen, China.
Hongfeng
H
Liao
Center for Clinical Laboratory, Xiamen University Affiliated Zhongshan Hospital, Xiamen, China.
Qing
Q
Hu
Center for Clinical Laboratory, Xiamen University Affiliated Zhongshan Hospital, Xiamen, China.
Chunlei
C
Ye
Center for Clinical Laboratory, Xiamen University Affiliated Zhongshan Hospital, Xiamen, China.
Yizhen
Y
Fang
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.
Qing
Q
Luo
Center for Clinical Laboratory, Xiamen University Affiliated Zhongshan Hospital, Xiamen, China.
Zhiyuan
Z
Lin
Department of Pathology, Xiamen University Affiliated Zhongshan Hospital, Xiamen, China. Electronic address: panchao123a@126.com.
Chao
C
Pan
Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX, United States. Electronic address: fwang@ibt.tmc.edu.
Fen
F
Wang
Center for Clinical Laboratory, Xiamen University Affiliated Zhongshan Hospital, Xiamen, China; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China. Electronic address: zhangzy1121@xmu.edu.cn.
Zhong-Ying
ZY
Zhang
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000401:mortality / Q000473:pathology*; D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D045325:HCT116 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D051820:TCF Transcription Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000737:chemistry / Q000378:metabolism*
D051820:TCF Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin; C466365:DHX32 protein, human; D053487:DEAD-box RNA Helicases
Angiogenesis; Colorectal cancer; DHX32; VEGFA; β-catenin