An extracellular matrix stiffness-induced breast cancer cell transcriptome resembles the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC).

Identifying mechanisms driving the transition from ductal carcinoma in situ (DCIS) to invasive breast cancer remains a challenge in breast cancer research. Breast cancer progression is accompanied by remodelling and stiffening of the extracellular matrix, leading to increased proliferation, survival, and migration. Here, we studied stiffness-dependent phenotypes in MCF10CA1a (CA1a) breast cancer cells cultured on hydrogels with stiffness corresponding to normal breast and breast cancer. This revealed a stiffness-associated morphology consistent with acquisition of an invasive phenotype in breast cancer cells. Surprisingly, this strong phenotypic switch was accompanied by relatively modest transcriptome-wide alterations in mRNA levels, as independently quantified using both DNA-microarrays and bulk RNA sequencing. Strikingly, however, the stiffness-dependent alterations in mRNA levels overlapped with those contrasting ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). This supports a role of matrix stiffness in driving the pre-invasive to invasive transition and suggests that mechanosignalling may be a target for prevention of invasive breast cancer.