Vasohibin-2 (VASH2): A Key Player In Cancer And Chemoresistance

Vasohibin-2 (VASH2) Promotes Cancer And Chemoresistance

 
cancer vasohibin
 

Basics

Vasohibin-2 (VASH2) is an angiogenesis promotor in the VASH family, along with vasohibin 1 (VASH1), and plays a role in tumor growth and chemotherapy resistance. R R

VASH1 plays the opposite role of VASH2 (inhibits angiogenesis) and is restricted to endothelial cells (ECs) and induced by the potent angiogenic factors VEGF and FGF-2. R R

Conditions With Increased VASH2 Activity

Increased VASH2:

  • Breast Cancer R R
  • Colon Cancer R
  • Liver Cancer R R
  • Hypoxia R
  • Ovarian Cancer R
  • Pancreatic Cancer R R
  • Prostate Cancer R
  • Pulminary Fibrosis R
  • Uterine Cancer R

Downsides Of Increased Vasohibin-2

1. Increases Tumor Growth

 
cancer vash-2
 

VASH2 increases angiogenesis and proliferation of cancer cells. R R

VASH2 is important for the creation of new cancer stem cells (via TGF-beta signalling). R R

For example, in triple-negative breast cancer (TNBC), high levels of VASH2 can help predict the aggressiveness of the cancer. R

In cell models of ovarain cancer, VASH-2 upregulated cells had larger tumors than controls. R

Inhibiting VASH2 may limit tumor growth and enhance apoptosis in tumor cells. R

For example, VASH2 antibiodies (to inhibit VASH2 expression) injected into human cancer cell cultures were just effective at suppressing cancer as the chemotherapy drug bevacizmab. R

High VASH2 expression may produce worse outcomes in cancer compared to those showing low VASH2 expression. R

2. Contributes To Chemoresistance

By downregulating p53 and other regulatory genes, VASH2 activity can decrease tumor sensitivity to chemotherapy drugs (chemoresistance). R R

For example, in hepatocellular carcinoma (HCC), increased VASH2 activity was able to inhibit the anti-tumor effects of the chemotherapy drug Cisplatin. R

In pancreatic cancer, increased VASH2 can inhibit the effects of the chemotherapy drug gemcitabine. R

Inhibiting VASH2 can reverse this and enhance chemosensitivy. R

How To Decrease VASH2

 
 

Supplements:

Drugs:

  • Ponatinib R

Pathways:

  • TGFβ-II receptor activation - blocks VASH2-mediated epithelial-mesenchymal transition (EMT) R
  • VASH1 R

What Pathways Increase VASH2?

Pathways:

  • HDAC inhibition (possibly downstream in analysis) R
  • PPARα (possibly downstream in analysis) R
  • TGFbeta-1 R

Mechanism Of Action

Simple:

  • Increases ABCC1 R
  • Increases ALDH1A1 R
  • Increases BCL-2 R
  • Increases CXCR4 R
  • Increases FGF-2 R R R
  • Increases GATA3 R
  • Increases GDF15 R
  • Increases HIF1alpha (in cow hair cells) R
  • Increases IGFBP3/6 R
  • Increases JUN R
  • Increases MMP2 R 
  • Increases Nanog R
  • Increases Oct4 R
  • Increases PAI-1 R
  • Increases RRM2 R
  • Increases Sox2 R
  • Increases TGF-β1 (ALK5) R
  • Increases VEGF R R
  • Increases Vimentin R
  • Increases ZEB1/2 R
  • Reduces Bax R
  • Reduces Caspase-3/6/9 R
  • Reduces CC-3 R
  • Reduces E-cadherin R
  • Reduces P53 R
  • Reduces VASH1 R

Advanced:

  • VASH2 is expressed in infiltrating mononuclear cells enhancing angiogenesis (mobilized from bone marrow to promote angiogenesis). R R
  • In the cell cycle, vuclear vasohibin-2 promotes cell proliferation by inducing G0/G1 to S phase progression. R
  • In HCC, VASH2 overexpression downregulates p53, the pro-apoptotic protein BCL2-associated X protein (Bax), and cleaved caspase-3 (CC-3) after treatment by CDDP. R
  • Induction of the Jun proto-oncogene (JUN) by VASH2 is responsible for upregulation of RRM2 expression. R
  • VASH2 upregulates stem cell markers such as ALDH1A1, Sox2, Oct4, Nanog, which reinforces VASH2 promotion of stem cell proportion. R
  • In breast cancer models, four growth factors activated by VASH2 were identified as follows: Fibroblast growth factor 2 (FGF2), growth/differentiation factor‑15 (GDF15), insulin‑like growth factor‑binding protein (IGFBP)3 and IGFBP6. R
  • By increasing the transcription factor of ESR1GATA-binding factor 3 (GATA3), VASH2 probably induces a shift towards TH2 response. R R

Genetics

VASH2

rs3002288

  • association with brown eyes R

More Research

  • VASH2 is higher after pregnancy in cows. R