Lipidomic and Membrane Mechanical Signatures in Triple-Negative Breast Cancer: Scope for Membrane-Based Theranostics.

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer associated with poor prognosis, higher grade, and a high rate of metastatic occurrence. Limited therapeutic interventions and the compounding issue of drug resistance in triple-negative breast cancer warrants the discovery of novel therapeutic targets and diagnostic modules. To this view, in addition to proteins, lipids also regulate cellular functions via the formation of membranes that modulate membrane protein function, diffusion, and their localization; thus, orchestrating signaling hot spots enriched in specific lipids/proteins on cell membranes. Lipid deregulation in cancer leads to reprogramming of the membrane dynamics and functions impacting cell proliferation, metabolism, and metastasis, providing exciting starting points for developing lipid-based approaches for treating TNBC. In this review, we provide a detailed account of specific lipidic changes in breast cancer, link the altered lipidome with membrane structure and mechanical properties, and describe how these are linked to subsequent downstream functions implicit in cancer progression, metastasis, and chemoresistance. At the fundamental level, we discuss how the lipid-centric findings in TNBC are providing cues for developing lipid-inspired theranostic strategies while bridging existing gaps in our understanding of the functional involvement of lipid membranes in cancer.