Adhesion strength and anti-tumor agents regulate vinculin of breast cancer cells

Abstract

The onset and progression of cancer are strongly associated with the dissipation of adhesion forces between cancer cells, thus facilitating their incessant attachment and detachment from the extracellular matrix (ECM) to move toward metastasis. During this process, cancer cells undergo mechanical stresses and respond to these stresses with membrane deformation while inducing protrusions to invade the surrounding tissues. Cellular response to mechanical forces is inherently related to the reorganization of the cytoskeleton, the dissipation of cell–cell junctions, and the adhesion to the surrounding ECM. Moreover, the role of focal adhesion proteins, and particularly the role of vinculin in cell attachment and detachment during migration, is critical, indicating the tight cell–ECM junctions, which favor or inhibit the metastatic cascade. The biomechanical analysis of these sequences of events may elucidate the tumor progression and the potential of cancer cells for migration and metastasis. In this work, we focused on the evaluation of the spreading rate and the estimation of the adhesion strength between breast cancer cells and ECM prior to and post-treatment with anti-tumor agents. Specifically, different tamoxifen concentrations were used for ER+ breast cancer cells, while even concentrations of trastuzumab and pertuzumab were used for HER2+ cells. Analysis of cell stiffness indicated an increased elastic Young’s modulus post-treatment in both MCF-7 and SKBR-3 cells. The results showed that the post-treatment spreading rate was significantly decreased in both types of breast cancer, suggesting a lower metastatic potential. Additionally, treated cells required greater adhesion forces to detach from the ECM, thus preventing detachment events of cancer cells from the ECM, and therefore, the probability of cell motility, migration, and metastasis was confined. Furthermore, post-detachment and post-treatment vinculin levels were increased, indicating tighter cell–ECM junctions, hence limiting the probability of cell detachment and, therefore, cell motility and migration.

Traction force with extracellular matrix mediated by cytoskeleton had an effect on metastasis through SLC8A1 induced Wnt-β-catenin pathway in endometrial cancer

“…Some study suggested that mechanical stimulus induced malignant behavior of tumor cells by regulating cytoskeletal signal pathway [22] . Adhesion forces between cells and ECM are correlated with vinculin levels, and increase of the vinculin limits the probability of cell detachment and, therefore, cell motility and migration [23] . Stimulation generated by the stiff substrates from ECM triggered the F-actin skeleton, resulting in viscosity decrease and migration of cancer cells [24] .…”

Vinculin Identified as a Potential Biomarker in Hand-Arm Vibration Syndrome Based on iTRAQ and LC–MS/MS-Based Proteomic Analysis

“…Conversely, the migratory cell ability is accompanied by a decrease in vinculin expression . In recent years, the downregulation of vinculin has been found in several highly metastatic cancer cells, which reminded us of its unique role in metastasis and relapse. − However, few efforts about vinculin were made in occupational diseases; the vinculin expression level in plasma has not been studied thoroughly compared with other tissues or cells, either. Plasma vinculin has the potential as the biomarker of atherosclerotic diseases, acute myocardial infarction, age-related macular degeneration, and irritable bowel syndrome (IBS), − but it was found to be upregulated in those diseases.…”

Long-term menopause exacerbates vaginal wall support injury in ovariectomized rats by regulating amino acid synthesis and glycerophospholipid metabolism

“…The DEGs that were found in patients with premature ovarian insufficiency were mainly associated with extracellular matrix (ECM)/structural organization, different types of junctions, and various catabolic/metabolic/biosynthetic processes. In addition, cytokine−cytokine receptor interactions, the PI3K-Akt signaling pathway, and the MAPK signaling pathway was also enriched, which have close regulatory effects on cellular mechanical properties ( 10 , 11 ). Zhu et al.…”