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Open AccessArticle

Circulating Tumor Cell Migration Requires Fibronectin Acting through Integrin B1 or SLUG

1
Department of Biological Sciences, Hunter College of The City University of New York, New York, NY 10065, USA
2
Department of Biology, The Graduate Center of The City University of New York, New York, NY 10016, USA
3
Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA
*
Author to whom correspondence should be addressed.
Cells 2020, 9(7), 1594; https://doi.org/10.3390/cells9071594
Received: 9 June 2020 / Revised: 27 June 2020 / Accepted: 30 June 2020 / Published: 1 July 2020
(This article belongs to the Special Issue Fibronectin in Health and Diseases)
Fibronectin (FN1) is an extracellular matrix protein gaining increasing attention for its multifaceted roles in cancer progression. Using our recently established circulating tumor cell (CTC) lines, we had demonstrated increased FN1 expression and enhanced migration in CTC lines, in comparison to primary tumor cell lines. Whether increased FN1 expression is directly required for CTC migration, and the specific role of FN1’s regulation of integrin B1 (ITGB1) and SLUG (SNAI2) in CTC migration remains unclear. Here, for the first time, we report that the knockdown of FN1, ITGB1, or SLUG expression in CTCs leads to a significant decrease in CTC migration. Knocking down two or all three of these proteins simultaneously did not further inhibit migration. We observed a corresponding increase in CTC migration when recombinant FN1 was added to CTCs. This effect was significantly impeded by prior knockdown of ITGB1 or SLUG. Using knock down experiments and western blotting analysis, we confirmed FN1’s regulation of ITGB1 and SLUG to occur via two separate, independent pathways. Consequently, we can conclude that FN1-dependent enhanced migration of CTCs requires downstream signaling through either ITGB1 or SLUG and that FN1 regulation of ITGB1 and SLUG may have important implications for cancer progression and metastasis. View Full-Text
Keywords: fibronectin (FN1); cancer cell migration; circulating tumor cells (CTCs); integrin B1 (ITGB1); SLUG (SNAI2); metastasis fibronectin (FN1); cancer cell migration; circulating tumor cells (CTCs); integrin B1 (ITGB1); SLUG (SNAI2); metastasis
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MDPI and ACS Style

Huaman, J.; Ogunwobi, O.O. Circulating Tumor Cell Migration Requires Fibronectin Acting through Integrin B1 or SLUG. Cells 2020, 9, 1594.

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