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. 2023 Apr;597(8):1098-1113.
doi: 10.1002/1873-3468.14531. Epub 2022 Nov 15.

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

Sofia De Marco  1 , Barbara Torsello  1 , Emanuela Minutiello  1 , Ivana Morabito  1 , Chiara Grasselli  1 , Silvia Bombelli  1 , Nicola Zucchini  2 , Giuseppe Lucarelli  3 , Guido Strada  4 , Roberto A Perego  1 , Cristina Bianchi  1
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Free article

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

Sofia De Marco et al. FEBS Lett. 2023 Apr.
Free article

Abstract

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.

Keywords: 3D culture; Abl2 tyrosine kinase; TGFβ signalling; clear cell Renal Cell Carcinoma; invasion.

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References

    1. Hagiwara N, Watanabe M, Iizuka-Ohashi M, Yokota I, Toriyama S, Sukeno M, et al. Mevalonate pathway blockage enhances the efficacy of mTOR inhibitors with the activation of retinoblastoma protein in renal cell carcinoma. Cancer Lett. 2018;431:182-9. https://doi.org/10.1016/j.canlet.2018.05.025
    1. Di J, Gao K, Qu D, Wu Y, Yang J, Zheng J. Rap2B promotes angiogenesis via PI3K/AKT/VEGF signaling pathway in human renal cell carcinoma. Tumor Biol. 2017;39:1-11. https://doi.org/10.1177/1010428317701653
    1. Motzer RJ, Escudier B, Gannon A, Figlin RA. Sunitinib: ten years of successful clinical use and study in advanced renal cell carcinoma. Oncologist. 2017;22:41-52. https://doi.org/10.1634/theoncologist.2016-0197
    1. Hsieh JJ, Purdue MP, Signoretti S, Swanton C, Albiges L, Schmidinger M, et al. Renal cell carcinoma. Nat Rev Dis Primers. 2018;3:1-19. https://doi.org/10.1038/nrdp.2017.9
    1. Rankin EB, Giaccia AJ. Hypoxic control of metastasis. Science. 2016;352:175-80. https://doi.org/10.1126/science.aaf4405

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