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CRISPR/Cas9-mediated Bag-1 knockout increased mesenchymal characteristics of MCF-7 cells via Akt hyperactivation-mediated actin cytoskeleton remodeling

Author

Listed:
  • Pelin Ozfiliz Kilbas
  • Nisan Denizce Can
  • Tugba Kizilboga
  • Fikret Ezberci
  • Hamdi Levent Doganay
  • Elif Damla Arisan
  • Gizem Dinler Doganay

Abstract

Bag-1 protein is a crucial target in cancer to increase the survival and proliferation of cells. The Bag-1 expression is significantly upregulated in primary and metastatic cancer patients compared to normal breast tissue. Overexpression of Bag-1 decreases the efficiency of conventional chemotherapeutic drugs, whereas Bag-1 silencing enhances the apoptotic efficiency of therapeutics, mostly in hormone-positive breast cancer subtypes. In this study, we generated stable Bag-1 knockout (KO) MCF-7 breast cancer cells to monitor stress-mediated cellular alterations in comparison to wild type (wt) and Bag-1 overexpressing (Bag-1 OE) MCF-7 cells. Validation and characterization studies of Bag-1 KO cells showed different cellular morphology with hyperactive Akt signaling, which caused stress-mediated actin reorganization, focal adhesion decrease and led to mesenchymal characteristics in MCF-7 cells. A potent Akt inhibitor, MK-2206, suppressed mesenchymal transition in Bag-1 KO cells. Similar results were obtained following the recovery of Bag-1 isoforms (Bag-1S, M, or L) in Bag-1 KO cells. The findings of this study emphasized that Bag-1 is a mediator of actin-mediated cytoskeleton organization through regulating Akt activation.

Suggested Citation

  • Pelin Ozfiliz Kilbas & Nisan Denizce Can & Tugba Kizilboga & Fikret Ezberci & Hamdi Levent Doganay & Elif Damla Arisan & Gizem Dinler Doganay, 2022. "CRISPR/Cas9-mediated Bag-1 knockout increased mesenchymal characteristics of MCF-7 cells via Akt hyperactivation-mediated actin cytoskeleton remodeling," PLOS ONE, Public Library of Science, vol. 17(1), pages 1-22, January.
    • Handle: RePEc:plo:pone00:0261062
    DOI: 10.1371/journal.pone.0261062
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