Journal of Preventive Medicine

Cancer Cells Profoundly Reprogrammed Their Metabolic Pathways

In breast cancer research, it is still difficult to determine the factors that lead to the development of invasive breast cancer from Ductal Carcinoma In Situ (DCIS). The extracellular matrix undergoes remodelling and stiffening as breast cancer progresses, resulting in increased proliferation, survival, and migration. MCF10CA1a (CA1a) breast cancer cells cultured on hydrogels with stiffness corresponding to normal breast and breast cancer were the subjects of our investigation to investigate stiffnessdependent phenotypes. This revealed a stiffness-related morphology that was consistent with breast cancer cells acquiring an invasive phenotype. As independently quantified with DNA-microarrays and bulk RNA sequencing, this significant phenotypic shift was accompanied by relatively minor transcriptome-wide mRNA levels. However, the stiffness-dependent alterations in mRNA levels shared striking similarities with those of invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS). Mechanosignalling may be a target for the prevention of invasive breast cancer, as this suggests that matrix stiffness plays a role in driving the transition from pre-invasive to invasive. Cancer cells profoundly reprogrammed their metabolic pathways in order to meet the requirements for energy and building blocks for rapid proliferation, particularly in tumor microenvironments lacking oxygen and nutrients. However, tumorigenesis and metastasis of cancer cells still require functional mitochondria and mitochondria-dependent oxidative phosphorylation. Comparing breast tumors to adjacent non-cancerous tissues, we demonstrate that mitochondrial elongation factor 4 (mtEF4) is significantly elevated in breast tumors, which is associated with tumor progression and poor prognosis.

Author(s): Tomas lee

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