Metabolic Signatures of Breast Cancer Subtypes and the Metabolic Impact of Chemotherapy

TL;DR

This study explores how different breast cancer subtypes use energy and how chemotherapy affects their metabolism.

Contribution

The study identifies unique metabolic signatures in breast cancer subtypes and their response to chemotherapy.

Findings

TNBC and metastatic cells show increased glycolytic and anaerobic metabolism.

ER+/PR+ cells exhibit high glucose use and sensitivity to metabolic effectors and doxorubicin.

Cancer cells differ from controls in nucleoside and amino acid utilization, especially in TNBC and metastatic lines.

Abstract

Background/Objectives: Breast cancer is a prevalent and heterogeneous disease with multiple subtypes, which are defined by characteristics such as molecular biomarkers and metastatic status. This study aimed to profile the metabolic activity of various breast cancer subtypes, both with and without chemotherapy (doxorubicin) application. Methods: Six human breast cell lines were evaluated, two non-tumorigenic controls and four cancerous lines. The cancer lines were clustered as primary-derived, metastasis-derived, triple-negative (TNBC), and strong hormone receptor-positive (ER+/PR+) and analyzed using the Biolog phenotype mammalian microarrays (PM-M1 to PM-M8) to assess metabolic activity via NADH production under a wide array of substrate parameters. Results: Unique metabolic profiles emerged across the subtypes and clusters; the TNBC and metastatic cells demonstrated enhanced utilization of glycolytic and anaerobic substrates consistent with the Warburg effect. The ER+/PR+ cells showed heightened glucose utilization and unique sensitivity to metabolic effectors and doxorubicin. Additionally, significant metabolic differences were observed in nucleoside and amino acid utilization between cancer and control cells, particularly in metastatic and TNBC lines. Conclusions: Our findings reveal the profound metabolic diversity among breast cancer subtypes and highlight distinct substrate dependencies for proliferation. The results additionally provide a framework for developing metabolic biomarkers and targeted therapies for chemotherapy resistance in breast cancer subtypes.

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