Stiff for the stride and soft for the glide: dual role of cytoskeleton in stiffness dynamics of breast cancer cell lines-a meta-analysis.

Estimation of cell stiffness has assumed significance as their difference in cancer and normal cells is being exploited for diagnostic and therapeutic purposes. However, the cell stiffness values reported (in terms of elastic modulus (E)) are largely varied even within the same cell line, hindering their exploitation. The current study aims to dissect and understand the various parameters resulting in these differences. Based on the analysis of E values reported from 1992 to 2025, it is found that the stiffness of breast cancer cell lines decreases in the order MCF-10A > MCF-7 > MDA-MB-231. The effect of anti-cancer strategies on cell stiffness reveals the important role played by the remodeling of the cytoskeleton. The dual role played by the cytoskeleton in maintaining the required stiffness and deformability in cancer cells based on biological conditions is consistently observed through the analyzed studies. The forest plots synthesized propose that although increasing and decreasing the stiffness of cancer cells is a treatment strategy, more studies focus on decreasing the stiffness of cancer cells to limit metastasis. The trend of variation in cell stiffness urges us to hypothesize the existence of a threshold range for mean stiffness values in cancer cells. The insights obtained can serve as a framework for studies related to the stiffness of breast cancer cells and aid researchers in making meaningful assessments of the obtained E values-a criterion emerging as a major player in cancer diagnosis.