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StarD13 differentially regulates migration and invasion in prostate cancer cells

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Abstract

Prostate cancer is the second most commonly diagnosed cancer in men and one of the main leading causes of cancer deaths among men worldwide. Rapid uncontrolled growth and the ability to metastasize to other sites are key hallmarks in cancer development and progression. The Rho family of GTPases and its activators the GTPase-activating proteins (GAPs) are required for regulating cancer cell proliferation and migration. StarD13 is a GAP for Rho GTPases, specifically for RhoA and Cdc42. We have previously shown that StarD13 acts as a tumor suppressor in astrocytoma as well as breast and colorectal cancer. In this study, we performed a functional comparative analysis of StarD13 targets/and or interacting molecules to understand the general role that StarD13 plays in cancers. Our data highlight the importance of StarD13 in modulating several hallmarks of cancer. Findings from database mining and immunohistochemistry revealed that StarD13 is underexpressed in prostate cancers, in addition knocking down Stard13 increased cancer cell proliferation, consistent with its role as a tumor suppressor. Stard13 depletion, however, led to an increase in cell adhesion, which inhibited 2D cell migration. Most interestingly, StarD13 depletion increases invasion and matrix degradation, at least in part, through its regulation of Cdc42. Altogether, the data presented suggest that StarD13 acts as a tumor suppressor inhibiting prostate cancer cell invasion.

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Fig. 1

source predicting the active interaction. Green: texmining, pink: experimentally determined, and blue: curated databases

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Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was funded by the Department of Natural Sciences at the Lebanese American University and by the School of Arts and Science Research and Development Council (SRDC) at LAU.

Funding

This work was supported by the Natural Science Department at the Lebanese American University and by the School of Arts and Science Research and Development Council (SRDC) at LAU.

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Authors and Affiliations

  1. Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Chouran, P.O. Box 13-5053, Beirut, 1102 2801, Lebanon

    Leila Jaafar, Isabelle Fakhoury, Sahar Saab & Mirvat El-Sibai

  2. Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon

    Layal El-Hajjar & Wassim Abou-Kheir

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  1. Leila Jaafar
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  2. Isabelle Fakhoury
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  3. Sahar Saab
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  4. Layal El-Hajjar
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  5. Wassim Abou-Kheir
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Contributions

LJ performed experiments and data analysis, IF performed experiments and data analysis and wrote the manuscript, SS performed experiments, WA-K provided intellectual and technical guidance, ME-S is the principal investigator who designed the study, provided funds, critical data analysis and discussion and edited the manuscript. All authors read and approved the final manuscript.

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Correspondence to Mirvat El-Sibai.

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Jaafar, L., Fakhoury, I., Saab, S. et al. StarD13 differentially regulates migration and invasion in prostate cancer cells. Human Cell 34, 607–623 (2021). https://doi.org/10.1007/s13577-020-00479-8

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