FAK family proteins regulatein vivobreast cancer metastasisviadistinct mechanisms DOI Open Access
Alessandro Genna, Joel Alter, Martina Poletti

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 29, 2023

ABSTRACT Breast cancer is the most commonly diagnosed malignancy and major leading cause of tumor-related deaths in women. It estimated that majority breast are a consequence metastasis, to which no cure exists at present. The FAK family proteins Proline-rich tyrosine kinase (PYK2) focal adhesion (FAK) highly expressed cancer, but exact cellular signaling mechanisms by they regulate vivo tumor cell invasiveness consequent metastatic dissemination mostly unknown. Using PYK2 knockdown xenograft model we show here, for first time, ablation either or decreases primary size significantly reduces Tumor MicroEnvironment Metastasis (TMEM) doorway activation, decreased intravasation reduced spontaneous lung metastasis. Intravital imaging analysis further demonstrates PYK2, not FAK, regulates motility phenotype switch between adhesion-mediated fast invadopodia-dependent, ECM-degradation associated slow within tumor. Furthermore, validate our intravital results with integrated transcriptomic proteomic data from tumors reveal new distinct pathways these two homologous kinases dissemination. Our findings identify as novel mediators mammary progression metastasis candidate therapeutic targets

Language: Английский

FAK family proteins regulatein vivobreast cancer metastasisviadistinct mechanisms DOI Open Access
Alessandro Genna, Joel Alter, Martina Poletti

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 29, 2023

ABSTRACT Breast cancer is the most commonly diagnosed malignancy and major leading cause of tumor-related deaths in women. It estimated that majority breast are a consequence metastasis, to which no cure exists at present. The FAK family proteins Proline-rich tyrosine kinase (PYK2) focal adhesion (FAK) highly expressed cancer, but exact cellular signaling mechanisms by they regulate vivo tumor cell invasiveness consequent metastatic dissemination mostly unknown. Using PYK2 knockdown xenograft model we show here, for first time, ablation either or decreases primary size significantly reduces Tumor MicroEnvironment Metastasis (TMEM) doorway activation, decreased intravasation reduced spontaneous lung metastasis. Intravital imaging analysis further demonstrates PYK2, not FAK, regulates motility phenotype switch between adhesion-mediated fast invadopodia-dependent, ECM-degradation associated slow within tumor. Furthermore, validate our intravital results with integrated transcriptomic proteomic data from tumors reveal new distinct pathways these two homologous kinases dissemination. Our findings identify as novel mediators mammary progression metastasis candidate therapeutic targets

Language: Английский

Citations

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