Oncotarget

Research Papers:

PDLIM4/RIL-mediated regulation of Src and malignant properties of breast cancer cells

Dmitry Sergeevich Kravchenko, Anna Evgenyevna Ivanova, Elizaveta Sergeevna Podshivalova and Stepan Petrovich Chumakov _

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Oncotarget. 2020; 11:22-30. https://doi.org/10.18632/oncotarget.27410

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Abstract

Dmitry Sergeevich Kravchenko1, Anna Evgenyevna Ivanova1, Elizaveta Sergeevna Podshivalova1 and Stepan Petrovich Chumakov1

1 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia

Correspondence to:

Stepan Petrovich Chumakov,email: hathkul@gmail.com

Keywords: RIL; PDLIM4; Src; breast cancer; metastases

Received: November 03, 2019     Accepted: December 16, 2019     Published: January 07, 2020

ABSTRACT

RIL/PDLIM4 gene was identified as a tumor suppressor, its expression is frequently altered in various types of malignancies. The product of RIL/PDLIM4 gene is an adapter protein involved in the actin cytoskeleton remolding and assembly of stress fibers crucial for cell motility and epithelial-mesenchymal transition. Although the exact mechanism tethering RIL to cancer development remains unknown some pieces of evidence suggest that RIL may act by suppressing activation of the proto-oncogene tyrosine-protein kinase Src. To further explore this issue we tested how different expression levels of RIL affected the activity of Src in breast cancer cell lines. RIL was ectopically overexpressed in the cell cultures with its relatively low endogenous level, or, otherwise, was downregulated by RNA interference. Whereas we observed no correlation between expression levels of RIL and activity of Src we found that in several cell lines elevated levels of RIL were associated with higher cell migratory activity along with the increased incidence of breast xenograft formation and metastasizing. The obtained data suggest that in some breast cancer models RIL may not act as Src kinase inhibitor, but rather play the role of a potential oncogene that promotes cell motility and contributes to cancer cells spreading.


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