Abstract B44: Keratin-associated protein 5-5 controls cytoskeletal function and cancer cell vascular invasion

Cancer cell vascular invasion is a crucial step in the malignant progression towards metastasis. Here we used a genome-wide RNAi screen with E0771 mammary cancer cells to uncover drivers of endothelial monolayer invasion. We identified keratin-associated protein 5-5 (Krtap5-5) as a candidate. Krtap5-5 belongs to large family of cysteine-rich proteins that is implicated in crosslinking keratin intermediate filaments during hair formation. To date, no role of these proteins in cancer has been reported. We found that depletion of Krtap5-5 from cancer cells led to cell blebbing, a loss of keratins 14 and 18 in addition to the upregulation of vimentin intermediate filaments. Krtap5-5 depletion did not impact cell viability but reduced cell motility and extravasation of cancer cells into tissues in a zebrafish model of extravasation. We conclude that Krtap5-5 is a previously unknown regulator of cytoskeletal function in cancer cells that modulates cell motility and vascular invasion. Citation Format: Eric B. Berens, Ghada M. Sharif, Marcel O. Schmidt, Casey W. Shuptrine, Louis M. Weiner, Eric Glasgow, Anna T. Riegel, Anton Wellstein. Keratin-associated protein 5-5 controls cytoskeletal function and cancer cell vascular invasion. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B44.