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- W2022382872 abstract "Metastasis accounts for the vast majority of cancer related deaths, yet the molecular mechanisms that drive metastatic spread remain poorly understood. Here we report that Tks5, which has been linked to formation of proteolytic cellular protrusions known as invadopodia, undergoes an isoform switch during metastatic progression in a genetically-engineered mouse model of lung adenocarcinoma. Non-metastatic primary tumor-derived cells predominantly expressed a short isoform Tks5 short , while metastatic primary tumor- and metastasis-derived cells acquired increased expression of the full-length isoform Tks5 long . This elevation of Tks5 long -to-Tks5 short ratio correlated with a commensurate increase in invadopodia activity in metastatic cells compared to non-metastatic cells. Further characterization of these isoforms by knockdown and over-expression experiments demonstrated that Tks5 long promoted invadopodia in vitro and increased metastasis in transplant models and an autochthonous model of lung adenocarcinoma. Conversely, Tks5 short decreased invadopodia stability and proteolysis, acting as a natural dominant-negative inhibitor to Tks5 long . Importantly, high Tks5 long and low Tks5 short expressions in human lung adenocarcinomas correlated with metastatic disease and predicted worse survival of early-stage patients. These data indicate that tipping the Tks5 isoform balance to a high Tks5 long -to-Tks5 short ratio promotes invadopodia-mediated invasion and metastasis. Citation Format: Carman Man-Chung Li, Guoan Chen, Talya Dayton, Caroline Kim-Kiselak, David Beer, Monte Winslow, Tyler Jacks. Differential Tks5 isoform expression contributes to metastatic invasion of lung adenocarcinoma. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C22." @default.
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- W2022382872 date "2013-10-01" @default.
- W2022382872 modified "2023-09-25" @default.
- W2022382872 title "Abstract C22: Differential Tks5 isoform expression contributes to metastatic invasion of lung adenocarcinoma" @default.
- W2022382872 doi "https://doi.org/10.1158/1538-7445.fbcr13-c22" @default.
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