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

Dmitry Sergeevich Kravchenko¹, Anna Evgenyevna Ivanova¹, Elizaveta Sergeevna Podshivalova¹

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

|February 1, 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.

Insights

The RIL/PDLIM4 gene, previously thought to be a tumor suppressor, may actually promote breast cancer cell migration and metastasis. Further research is needed to understand its role in malignancies.

Area of Science:

Oncology
Molecular Biology
Cell Biology

Background:

The RIL/PDLIM4 gene is recognized as a tumor suppressor with altered expression in malignancies.
Its protein product is an adapter protein involved in actin cytoskeleton remodeling and cell motility.
Evidence suggested RIL might suppress the proto-oncogene tyrosine-protein kinase Src.

Purpose of the Study:

To investigate the relationship between RIL/PDLIM4 expression levels and Src activity in breast cancer cell lines.
To explore the potential oncogenic role of RIL/PDLIM4 in breast cancer progression.

Main Methods:

Ectopic overexpression of RIL/PDLIM4 in breast cancer cell lines with low endogenous levels.
Downregulation of RIL/PDLIM4 using RNA interference.
Assessment of Src activity and cell migratory activity.
Evaluation of breast xenograft formation and metastasis incidence.

Main Results:

No correlation was observed between RIL/PDLIM4 expression levels and Src activity.
Elevated RIL/PDLIM4 levels were associated with increased cell migratory activity in several cell lines.
Higher incidence of breast xenograft formation and metastasis was observed with increased RIL/PDLIM4 levels.

Conclusions:

RIL/PDLIM4 may not function as a Src kinase inhibitor in all breast cancer contexts.
RIL/PDLIM4 could act as a potential oncogene promoting cell motility and metastasis in certain breast cancer models.
The role of RIL/PDLIM4 in cancer development requires further investigation.

Read full analysis

Keywords:

PDLIM4 RIL Src breast cancer metastases

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