The cross-talk between Abl2 tyrosine kinase and TGFβ1 signalling modulates the invasion of clear cell Renal Cell Carcinoma cells.
Sofia De MarcoBarbara TorselloEmanuela MinutielloIvana MorabitoChiara GrasselliSilvia BombelliNicola ZucchiniGiuseppe LucarelliGuido StradaRoberto A PeregoCristina BianchiPublished in: FEBS letters (2022)
Clear cell Renal Cell Carcinoma (ccRCC) is the most common and metastatic urological cancer. Molecular players of ccRCC progression and metastasis are not completely known. Here, using primary cell cultures from patients' specimens, we found that TGFβ1/Smad signalling is more activated in high versus low grade ccRCC and inversely correlates with Abl2 tyrosine kinase protein expression. TGFβ1 treatment increased ubiquitination and degradation of Abl2 protein in ccRCC cell lines by TGFβ1/Smad pathway activation and reactive oxygen species production. 3D invasion and matrix degradation assays showed that Abl2 promoted TGFβ1-induced ccRCC cell invasion and maturation of invadopodia, a hallmark of tumour invasion and metastasis. Our findings define Abl2 as a new downstream molecule of TGFβ1 signalling and putative target to counteract advanced ccRCC.
Keyphrases
- tyrosine kinase
- transforming growth factor
- epidermal growth factor receptor
- epithelial mesenchymal transition
- low grade
- reactive oxygen species
- cell migration
- squamous cell carcinoma
- ejection fraction
- small cell lung cancer
- prognostic factors
- stem cells
- patient reported outcomes
- high throughput
- cell therapy
- diabetic rats
- small molecule
- bone marrow
- endoplasmic reticulum stress
- urinary tract