ArticleBMC cancer2020
Hypoxic induction of vasculogenic mimicry in hepatocellular carcinoma: role of HIF-1 α, RhoA/ROCK and Rac1/PAK signaling.
Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 70 citations in OpenAlex.
- Hypoxia-inducible factor-1 (HIF-1) in the molecular mechanisms of liver fibrosis: research progress on its role and therapeutic strategies.Journal of applied genetics · 2026Review
- Review
- Spatial phosphoproteomics reveals regional phosphorylation features in liver cirrhosis progression.Journal of translational medicine · 2026Article
- The Design Strategies and Applications of Engineered Nanoparticles for Traumatic Brain Injury.International journal of nanomedicine · 2026Review
- Convergent Metabolic Pathways in MASH Therapeutics: An AMPK-Centric Analysis.Journal of cellular and molecular medicine · 2026Review
- Emerging strategies for targeting vasculogenic mimicry in breast cancer treatment.Discover oncology · 2025Review
- Wuweizisu B for cancer treatment from multitarget mechanisms to precision delivery strategies (Review).International journal of molecular medicine · 2025Review
- Vascular mimicry and mosaic vessels in parathyroid tumours: a new diagnostic approach?Journal of clinical pathology · 2025Article
- RHOA-dependent regulation of mitochondrial remodeling and cell motility in hypoxia-exposed gastric epithelial cells.Journal of cell science · 2025Article
- History of hypoxia exposure aids future cell invasion according to cell type and collagen density.Molecular biology of the cell · 2025Article
- Article
- A comprehensive review of Schisandrin B's preclinical antitumor activity and mechanistic insights from network pharmacology.Frontiers in pharmacology · 2025Review
- Hypoxia upregulates hepatic angiopoietin-2 transcription to promote the progression of hepatocellular carcinoma.World journal of hepatology · 2024Article
- RhoA-ROCK2 signaling possesses complex pathophysiological functions in cancer progression and shows promising therapeutic potential.Cancer cell international · 2024Review
- Review
- The role of N6-methyladenosine modification in tumor angiogenesis.Frontiers in oncology · 2024Review
- Lupeol and Paclitaxel cooperate in hindering hypoxia induced vasculogenic mimicry via suppression of HIF-1α-EphA2-Laminin-5γ2 network in human oral cancer.Journal of cell communication and signaling · 2023Article
- Melatonin regulates microglial polarization to M2 cell via RhoA/ROCK signaling pathway in epilepsy.Immunity, inflammation and disease · 2023Article
- Schisandrin B inhibits tumor progression of hepatocellular carcinoma by targeting the RhoA/ROCK1 pathway.Journal of gastrointestinal oncology · 2023Article
- P-21 Activated Kinases in Liver Disorders.Cancers · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundVasculogenic 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.
methodsKaplan-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.
resultsHIF-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.
conclusionsRhoA/ROCK and Rac/PAK signaling played crucial roles in hypoxia-induced VM via Ser72 and Ser56 Vimentin phosphorylation in HCC.
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