Browsing by Author "Rodrigues, Vanessa"
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- Demonstrating a role of paxillin in adherens junction strengthening and in premalignant to malignant progressionPublication . Rodrigues, Vanessa; Janody, Florence; Carvalhal, SaraBreast cancer poses a substantial threat to women worldwide, often preceded by premalignant lesions that hold potential for progression to invasive cancer. However, accurately predicting which premalignant lesions will progress remains a significant challenge. This study addresses this issue by unravelling the intricate interplay between adherens junctions (AJs) and focal adhesions (FAs) in the progression of premalignant breast cells to invasive cancer. Both AJs and FAs are complex, multifunctional protein assemblies linked to the actin cytoskeleton. Recent advancements in mass spectrometry and adhesion-specific enrichment techniques have elucidated hundreds of proteins constituting integrin and cadherin adhesomes. Nevertheless, these adhesomes compositions are highly variable across cell types and experimental conditions. Despite their traditional distinction, AJs and FAs share numerous signalling molecules, including Paxillin, and are mechanosensitive structures, capable of transducing mechanical cues into transcriptional regulation of cellular processes. Utilizing a human mammary epithelial cell line with conditional Src protooncogene activation, which recapitulates molecular processes in breast cancer progression, the CRC group demonstrated that before undergoing Epithelial to Mesenchymal transition, premalignant MCF10A-ER-Src cells experience a transient state characterized by actomyosin stress fiber accumulation associated with larger FAs, exclusively to cells with E-cadherin/P-cadherin-positive adherens junctions. This mechanical stiffening promotes cell proliferation and amplifies Src activation, propelling cells toward a fully transformed state. In this project we aimed to investigate the influence of Src activation on FA dynamics in premalignant MCF10A-ER-Src cells connected through AJs and to investigate the role of FA component Paxillin, in the progression from premalignant to malignant. The findings obtained are directly aligned with our previous research as the measurements performed on FAs unveils that Src activation triggers the assembly of larger FAs associated with polarized stress fibers in premalignant MCF10A-ER-Src cells connected through AJs. Alongside, we showed that knocking down Paxillin could be an effective tool to weaken FAs strengthening.