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

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 protooncogene 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.

Identification of novel gene signature predicting lymph node metastasis in papillary thyroid cancer via bioinformatics analysis and in vitro validation

“…Yanyan Jia et al demonstrated downregulated expression of PDLIM4 promoted ovarian cancer cells migratory and invasion by activating STAT3 signal pathway, which contributed to lymph node metastasis in ovarian cancer (Jia et al 2019). However, the high level of PDLIM4 in the speci c breast cancer cell lines (MDA-MB-231 and MDA-MB-436) had a higher cell migratory rate via increasing Src kinase activity as an oncogene (Kravchenko et al 2020), demonstrating the controversial and diversity function of PDLIM4. In addition, PDLIM4 was proved to be highly expressed and underwent hypermethylation in THCA (Jiang et al 2023), but the biological effect on lymph node metastasis in PTC was still unclear.…”

Prognostic signature of ovarian cancer based on 14 tumor microenvironment-related genes

“…[ 31 , 32 ] PDLIM4, a gene which is frequently suppressed in various cancers, is considered as a tumor suppressor. [ 33 ] It has been shown that PDLIM4 expression is significantly decreased in ovarian cancer, which is related to the aggressive characteristics of this disease such as the proliferation, migration, and invasion abilities of cancer cells, leading to an inferior prognosis. [ 34 ] ELN is significantly differentially expressed between primary ovarian cancer and peritoneal metastatic ovarian cancers, indicating that ELN may be associated with the metastasis of ovarian cancer.…”

“…COMP encodes the extracellular matrix glycoprotein, and its increased expression is implicated in the development of epithelial ovarian cancer involving in the proliferation, migration, invasion, and apoptosis of ovarian cancer cells regulated by SNHG25 [31,32] . PDLIM4, a gene which is frequently suppressed in various cancers, is considered as a tumor suppressor [33] . It has been shown that PDLIM4 expression is significantly decreased in ovarian cancer, which is related to the aggressive characteristics of this disease such as the proliferation, migration, and invasion abilities of cancer cells, leading to an inferior prognosis [34] .…”

PDZ and LIM Domain-Encoding Genes: Their Role in Cancer Development

“…Feng et al found that PDLIM4 was highly methylated in tumor tissue by analyzing 38 pairs of patients with primary BC lymphatic metastases [129], and other studies showed that PDLIM4 expression was negatively correlated with tumor size, differentiation status, and SPF (S-phase fraction) value [130]. However, it has also been shown that upregulation of PDLIM4 expression promotes BC cell migration [131]. Proper assessment of its role in the malignant progression of BC facilitates the implementation of individualized tumor treatment.…”