American Association for Cancer Research
crc-22-0394-s02.pdf (5.3 MB)

Supplementary Figure S2 from Mitochondrial metabolism drives low-density lipoprotein-induced breast cancer cell migration

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journal contribution
posted on 2023-04-04, 13:45 authored by Sandrina Nóbrega-Pereira, Francisco Santos, Miguel Oliveira Santos, Teresa L. Serafim, Ana Patrícia Lopes, Diogo Coutinho, Filipa S. Carvalho, Rosário M. Domingues, Pedro Domingues, Bruno Bernardes de Jesus, Vanessa A Morais, Sérgio Dias

LDL exposure induces mitochondrial network spread distribution and destabilized cristae in migrating breast cancer cells. Related to Fig. 2



Most cancer related deaths are due to metastases. Systemic factors, such as lipid-enriched environments (as low-density lipoprotein (LDL)-cholesterol), favor breast cancer, including triple negative breast cancer (TNBC) metastasis formation. Mitochondria metabolism impacts TNBC invasive behavior but its involvement in a lipid-enriched setting is undisclosed. Here we show that LDL increases lipid droplets, induces CD36 and augments TNBC cells migration and invasion in vivo and in vitro. LDL induces higher mitochondrial mass and network spread in migrating cells, in an actin remodeling-dependent manner, and transcriptomic and energetic analyses revealed that LDL renders TNBC cells dependent on fatty acids (FAs) usage for mitochondrial respiration. Indeed, engagement on FA transport into the mitochondria is required for LDL-induced migration and mitochondrial remodeling. Mechanistically, LDL treatment leads to mitochondrial long chain fatty acid (LCFA) accumulation and increase reactive oxygen species (ROS) production. Importantly, CD36 or ROS blockade abolished LDL-induced cell migration and mitochondria metabolic adaptations. Our data suggest that LDL induces TNBC cells migration by reprogramming mitochondrial metabolism, revealing a new vulnerability in metastatic breast cancer.