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

In this post, we will dicuss how vasohibin-2 (VASH2) plays a role cancer progression and chemoresistance.

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

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

1. Increases Tumor Growth

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

Supplements:

• Garcinia (Gambogic Acid) R

Drugs:

• Ponatinib R

Pathways:

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

Pathways:

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

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 ESR1, GATA-binding factor 3 (GATA3), VASH2 probably induces a shift towards TH2 response. R R

VASH2

rs3002288

• association with brown eyes R

• VASH2 is higher after pregnancy in cows. R