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

ABSTRACT: 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-1?), 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-1? small interfering RNA (siRNA), overexpressed or short hairpin RNA (shRNA) of ROCK and kinase inhibitors were used to explore the effect of HIF-1?, RhoA/ROCK, Rac1/PAK and Vimentin on VM. RESULTS:HIF-1? or Vimentin was upregulated in VM+ HCC tissues, compared to non-cancerous tissues (P?

SUBMITTER: Zhang JG 

PROVIDER: S-EPMC6958789 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature