Fig. 5
ETV5 in cancer biology. A ETV5 in cell mobility and EMT. ETV5 mediates the invasive phenotype through a BDNF-TrkB-ERK-ETV5-BDNF loop. epidermal growth factor receptor (EGFR)-LPP signaling promotes zinc finger E-Box binding homeobox factors 1 (ZEB1) expression through ETV5. ETV5 transcriptionally regulates the expression of TAFAZZIN (TAZ), twist family BHLH transcription factors 1 (TWIST), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), Vimentin, N-Cadherin and E-Cadherin. ETV5 upregulates NID1, fibronectin (FN), α5-integrin and β1-integrin to promote cancer cell adherence to laminin and collagens. ETV5 promotes spindle and kinetochore associated complex subunit 1 (SKA1) and transient receptor potential cation channel subfamily V member 2 (TRPV2) expression to upregulate MMP2 and MMP9, which degrade collagens to promote invasion through the ECM. B ETV5 in angiogenesis: ETV5 upregulates the mRNA expression of VEGFA, PDGF-BB and Cadherin 5 (CDH5). CDH5 promotes angiogenesis through the upregulation of MMP9. In an autocrine manner, PDGF-BB activates the ERK/MAPK and STAT3 to upregulate ETV5, VEGFA and CCL2. PDGF-BB, VEGFA and CCL2 activate ERK/MAPK, PI3K/AKT and p38/MAPK signaling in endothelial cells in a paracrine manner. C ETV5 in cell cycle: FGFs activate ETV5 via an ERK/MAPK-dependent pathway. Activated ETV5 promotes the G1/S and G2/M transition by enhancing E2F1 and FOXM1 transcription. Furthermore, ETV5 suppress the binding of p21 to CDK2/4 and Cyclin D/E, contributing to the phosphorylation of p130 and promoting the G1/S transition. Moreover, E2F1 induces chromatin assembly factor 1 subunit A/B (CHAF1B) to decrease DUX4 expression, which promotes p21 activity and cell cycle arrest. D ETV5 in oxidative stress: In Hec-1 A endometrial cancer, H2O2 promotes ETV5 and DHRS2 expression, resulting in increased ROS levels. In ovarian cancer, ETV5 upregulates the expression of FOXM1, which protects cells from oxidative stress. EGF epidermal growth factor, CCR2 C-C motif chemokine receptor 2, Src nonreceptor tyrosine kinase