The cross ‐talk between Abl2 tyrosine kinase and TGFβ1 signalling modulates the invasion of clear cell Renal Cell Carcinoma cells

Our data show that the axis TGF β1/Abl2 plays an important role in the invasion of clear cell Renal Cell Carcinoma (ccRCC) cells, a key aspect of the metastatic disease, through invadopodia formation. These findings suggest that the inhibition of Abl2 can counteract the invasive process and can be a promising strategy against ccR CC. 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 TGF β1/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 prod uction. 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 adv anced ccRCC.
Source: FEBS Letters - Category: Biochemistry Authors: Tags: Research Article Source Type: research