Cpt1c Downregulation Causes Plasma Membrane Remodelling and Anthracycline Resistance in Breast Cancer
Muley, Helena (Universitat Internacional de Catalunya)
Valencia, Karmele (Universidad de Navarra)
Casas, Josefina (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Moreno, Bea (Universidad de Navarra)
Botella, Luis (Universitat Internacional de Catalunya. Departament de Ciències Bàsiques)
Lecanda, Fernando (Universidad de Navarra)
Fadó, Rut (Universitat Autònoma de Barcelona. Institut de Neurociències)
Casals, Nuria (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)

Date:	2023
Abstract:	Breast cancer (BC) is the most common malignancy in women worldwide. While the main systemic treatment option is anthracycline-containing chemotherapy, chemoresistance continues to be an obstacle to patient survival. Carnitine palmitoyltransferase 1C (CPT1C) has been described as a poor-prognosis marker for several tumour types, as it favours tumour growth and hinders cells from entering senescence. At the molecular level, CPT1C has been associated with lipid metabolism regulation and important lipidome changes. Since plasma membrane (PM) rigidity has been associated with reduced drug uptake, we explored whether CPT1C expression could be involved in PM remodelling and drug chemoresistance. Liquid chromatography-high resolution mass spectrometry (LC-HRMS) lipid analysis of PM-enriched fractions of MDA-MB-231 BC cells showed that CPT1C silencing increased PM phospholipid saturation, suggesting a rise in PM rigidity. Moreover, CPT1C silencing increased cell survival against doxorubicin (DOX) treatment in different BC cells due to reduced drug uptake. These findings, further complemented by ROC plotter analysis correlating lower CPT1C expression with a lower pathological complete response to anthracyclines in patients with more aggressive types of BC, suggest CPT1C as a novel predictive biomarker for BC chemotherapy.
Grants:	Agencia Estatal de Investigación PID2020-114953RB-C22
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	CPT1C ; Chemoresistance ; Drug uptake ; Breast cancer ; Doxorubicin ; Plasma membrane ; Lipid remodelling ; Fatty acid saturation
Published in:	International journal of molecular sciences, Vol. 24 (january 2023) , ISSN 1422-0067

DOI: 10.3390/ijms24020946
PMID: 36674468

18 p, 4.1 MB

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