Profilin‐1 overexpression restores adherens junctions in MDA‐MB‐231 breast cancer cells in R‐cadherin‐dependent manner

Abstract

Profilin-1 (Pfn1), a ubiquitously expressed actin-binding protein, is downregulated in several different types of adenocarcinoma and elicits tumor-suppressive effect on breast cancer cell lines. MDA-MB-231 (MDA-231), a breast cancer cell line that displays all the characteristics of postepithelial-to-mesenchymal transition and does not form cell-cell adhesion, can be reverted to an epithelioid phenotype by Pfn1 overexpression. This morphological transition is caused by restoration of adherence junctions (AJ) requiring Pfn1's interaction with actin. Pfn1 overexpression increases the expression level of R-cadherin (a type of cadherin that is endogenously expressed in the parental cell line) and restores AJ in MDA-231 cells in R-cadherin dependent manner. These findings highlight important role of Pfn1 in the regulation of epithelial cell-cell adhesion.

Profilin-1 downregulation has contrasting effects on early vs late steps of breast cancer metastasis

“…Immunostaining of β-catenin in HUVEC/MDA-231 co-culture was performed according to the published protocol. 36 Images of stained cells were acquired with a ×20 objective on an Olympus IX-71 epifluorescence microscope (Olympus America, Center Valley, PA, USA).…”

Quantitative Proteomic Analysis in Metastatic Renal Cell Carcinoma Reveals a Unique Set of Proteins with Potential Prognostic Significance

“…In addition, Gal-1 enhances the activation of Cdc42, increasing the number and length of filopodia on tumor cells (40). Dysregulated Pfn1 has been previously reported to be involved in the restoration of adherent junctions in breast cancer cells (41), and galectin-3 (Gal-3) has been shown to be involved in breast cancer cell adhesion (42). The identified proteins also have an effect on cellular migration, as S100A11 has been shown to mediate hypoxia-induced mitogenic factor-induced smooth muscle cell migration (43), and both 14 -3-3 (44) and vimentin (45) have been shown to be involved in cellular migration.…”

Role of the actin-binding protein profilin1 in radial migration and glial cell adhesion of granule neurons in the cerebellum

“…Interestingly, defective cell migration upon profilin1 manipulation is associated with impaired formation of focal adhesions and adherence junctions suggesting that primary defects in cellmatrix and cell-cell adhesions contribute to the observed migration phenotypes. 15,21,23 Both the actin and the poly-L-proline binding domains of profilin1 appear to be important for cell migration. 16 Poly-L-proline ligands of profilin1 that are of particular relevance for cell adhesion and migration are those directly involved in cytoskeletal dynamics such as members of the Ena/VASP protein family or the Rac/Rho effectors WASP (Wiskott-Aldrich syndrome protein), WAVE (WASP family verprolin-homologous protein) and mDia (mammalian diaphanous).…”