Hypoxia-induced vasculogenic mimicry formation in human colorectal cancer cells: Involvement of HIF-1a, Claudin-4, and E-cadherin and Vimentin

Li, Wen; Zong, Shaoqi; Shi, Qi; Li, HongJia; Xu, Jian; Hou, Fenggang

doi:10.1038/srep37534

Cited by 75 publications

(60 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1). This observation is in accordance with previous work by Li, et al, who reported particularly HIF-1α -induced vasculogenic mimicry formation in human colorectal cancer cells [30].…”

Section: Discussionsupporting

confidence: 94%

Hypoxic induction of vasculogenic mimicry in hepatocellular carcinoma: role of HIF-1 α, RhoA/ROCK and Rac1/PAK signaling

Zhang

et al. 2020

BMC Cancer

View full text Add to dashboard Cite

Background: Vasculogenic mimicry (VM), defined as a capability of aggressive tumor Cells to mimic embryonic vasculogenic networks, caused poor prognosis in hepatocellular carcinoma (HCC). Rho kinases (ROCK), p21-activated kinase (PAK), hypoxia or epithelial-mesenchymal transition (EMT) contributed to the VM potential. However, the details underlying these biological behaviors have not been completely elucidated. Methods: Kaplan-Meier analysis was conducted to predict relationship with hypoxia Inducible factor (HIF-1α), EMT related markers: Vimentin and patient prognosis. CD34/periodic acid-Schiff (PAS) double staining was examined to differentiate VM-positive (VM+) and VM-negative (VM-) samples. Cells were cultured under controlled hypoxic environments (1% O2) or normoxic conditions. The effect of hypoxia on RhoA/ROCK, Rac1/PAK and EMT were evaluated by real time-qPCR and western blot. HIF-1α small interfering RNA (siRNA), overexpressed or short hairpin RNA (shRNA) of ROCK and kinase inhibitors were used to explore the effect of HIF-1α, RhoA/ROCK, Rac1/PAK and Vimentin on VM. Results: HIF-1α or Vimentin was upregulated in VM+ HCC tissues, compared to non-cancerous tissues (P < 0.01), and patients with high expression of HIF-1α or Vimentin had worse prognosis (P < 0.001). We showed hypoxia induced RhoA/ROCK and Rac1/PAK signaling transduction, and EMT could be repressed by HIF-1α siRNA. Notably, RhoA/ROCK or Rac1/PAK stabilized HIF-1α in hypoxia, whereas HIF-1α did not significantly altered RhoA/ROCK or Rac1/PAK signaling in hypoxia. Moreover, we found distinct roles of ROCK1, ROCK2 and PAK in regulating Vimentin phosphorylation. Conclusions: RhoA/ROCK and Rac/PAK signaling played crucial roles in hypoxia-induced VM via Ser72 and Ser56 Vimentin phosphorylation in HCC.

show abstract

“…1). This observation is in accordance with previous work by Li, et al, who reported particularly HIF-1α -induced vasculogenic mimicry formation in human colorectal cancer cells [30].…”

Section: Discussionsupporting

confidence: 94%

Hypoxic induction of vasculogenic mimicry in hepatocellular carcinoma: role of HIF-1 α, RhoA/ROCK and Rac1/PAK signaling

Zhang

et al. 2020

BMC Cancer

View full text Add to dashboard Cite

show abstract

“…Moreover, VM is associated with high tumor grade, invasion, metastasis, and poor prognosis in patients with malignant tumors [3][4][5][6]. In recent years, VM has been reported in a variety of malignant tumors, such as melanoma, glioblastoma, osteosarcoma, hepatocellular carcinoma (HCC), breast cancer, lung cancer, gastric cancer, colorectal cancer, and prostate cancer [7][8][9][10][11][12][13][14][15][16][17][18][19]. VM has emerged as a promising new target for anti-tumor therapy [20,21].…”

Section: Introductionmentioning

confidence: 99%

Vasculogenic mimicry in carcinogenesis and clinical applications

et al. 2020

View full text Add to dashboard Cite

Distinct from classical tumor angiogenesis, vasculogenic mimicry (VM) provides a blood supply for tumor cells independent of endothelial cells. VM has two distinct types, namely tubular type and patterned matrix type. VM is associated with high tumor grade, tumor progression, invasion, metastasis, and poor prognosis in patients with malignant tumors. Herein, we discuss the recent studies on the role of VM in tumor progression and the diverse mechanisms and signaling pathways that regulate VM in tumors. Furthermore, we also summarize the latest findings of non-coding RNAs, such as lncRNAs and miRNAs in VM formation. In addition, we review application of molecular imaging technologies in detection of VM in malignant tumors. Increasing evidence suggests that VM is significantly associated with poor overall survival in patients with malignant tumors and could be a potential therapeutic target.

show abstract

“…7 VM had been found to evaluate in various aggressive cancers, including colorectal cancer, 8 breast cancer, 9 melanoma, 10 and head and neck squamous cell carcinoma, 11 suggesting that it was a novel hallmark of cancer. 17 Moreover, Ahluwalia et al reported that HIF-1 by hypoxia condition adjusted vascular endothelial growth factor A (VEGFA) expression at the transcriptional level. 12 Recently, increasing evidence has showed that hypoxic microenvironment not only accelerated tumour invasion and metastasis, but also led to VM formation 13,14 and the expression of hypoxia-inducible factor-1α (HIF-1α) was associated with VM in many cancers types, including breast cancer, 15 ovarian cancer 16 and colorectal cancer.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia promotes vasculogenic mimicry formation by vascular endothelial growth factor A mediating epithelial‐mesenchymal transition in salivary adenoid cystic carcinoma

Wang

Zheng

et al. 2019

Cell Proliferation

View full text Add to dashboard Cite

Objectives To investigate the role of hypoxia in vasculogenic mimicry (VM) of salivary adenoid cystic carcinoma (SACC) and the underlying mechanism involved. Materials and methods Firstly, wound healing, transwell invasion, immunofluorescence and tube formation assays were performed to measure the effect of hypoxia on migration, invasion, EMT and VM of SACC cells, respectively. Then, immunofluorescence and RT‐PCR were used to detect the effect of hypoxia on VE‐cadherin and VEGFA expression. And pro‐vasculogenic mimicry effect of VEGFA was investigated by confocal laser scanning microscopy and Western blot. Moreover, the levels of E‐cadherin, N‐cadherin, Vimentin, CD44 and ALDH1 were determined by Western blot and immunofluorescence in SACC cells treated by exogenous VEGFA or bevacizumab. Finally, CD31/ PAS staining was performed to observe VM and immunohistochemistry was used to determine the levels of VEGFA and HIF‐1α in 95 SACC patients. The relationships between VM and clinicopathological variables, VEGFA or HIF‐1α level were analysed. Results Hypoxia promoted cell migration, invasion, EMT and VM formation, and enhanced VE‐cadherin and VEGFA expression in SACC cells. Further, exogenous VEGFA markedly increased the levels of N‐cadherin, Vimentin, CD44 and ALDH1, and inhibited the expression of E‐cadherin, while the VEGFA inhibitor reversed these changes. In addition, VM channels existed in 25 of 95 SACC samples, and there was a strong positive correlation between VM and clinic stage, distant metastases, VEGFA and HIF‐1α expression. Conclusions VEGFA played an important role in hypoxia‐induced VM through regulating EMT and stemness, which may eventually fuel the migration and invasion of SACC.

show abstract

Hypoxia-induced vasculogenic mimicry formation in human colorectal cancer cells: Involvement of HIF-1a, Claudin-4, and E-cadherin and Vimentin

Cited by 75 publications

References 22 publications

Hypoxic induction of vasculogenic mimicry in hepatocellular carcinoma: role of HIF-1 α, RhoA/ROCK and Rac1/PAK signaling

Hypoxic induction of vasculogenic mimicry in hepatocellular carcinoma: role of HIF-1 α, RhoA/ROCK and Rac1/PAK signaling

Vasculogenic mimicry in carcinogenesis and clinical applications

Hypoxia promotes vasculogenic mimicry formation by vascular endothelial growth factor A mediating epithelial‐mesenchymal transition in salivary adenoid cystic carcinoma

Contact Info

Product

Resources

About