Francisco Santos

Universidade Federal de Mato Grosso

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Bruno Bernardes de Jesus

University of Aveiro

Sandrina Nóbrega‐Pereira

University of Aveiro

M. Rosário M. Domingues

University of Aveiro

Ana Patrícia Lopes

University of Lisbon

Diogo Coutinho

Instituto de Medicina Molecular João Lobo Antunes

Miguel Oliveira Santos

University of Lisbon

Pedro Domíngues

University of Aveiro

Vanessa A. Morais

University of Lisbon

Teresa L. Serafim

University of Lisbon

Filipa S. Carvalho

University of Lisbon

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University of Lisbon

Universidade de São Paulo

University of Aveiro

Universidade Federal de Pernambuco

Universidade Federal de Mato Grosso

Universidade Federal de Minas Gerais

Universidade Federal do Acre

Universidade Federal de Jataí

Instituto Butantan

Instituto de Medicina Molecular João Lobo Antunes

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Supplementary Figure S5 from Mitochondrial metabolism drives low-density lipoprotein-induced breast cancer cell migration

Sandrina Nóbrega‐Pereira Francisco Santos Miguel Oliveira Santos Teresa L. Serafim Ana Patrícia Lopes

LDL-induced migratory behavior of TNBC cells relies on fatty acid transport into the mitochondria. Related to Fig. 5

Low-density lipoprotein

Triple-negative breast cancer

10.1158/2767-9764.22551332

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Supplementary Figure S7 from Mitochondrial metabolism drives low-density lipoprotein-induced breast cancer cell migration

Sandrina Nóbrega‐Pereira Francisco Santos Miguel Oliveira Santos Teresa L. Serafim Ana Patrícia Lopes

¬Reactive oxygen species formation downstream of mitochondria fatty acid entry is required for LDL-induced migration of breast cancer cells. Related to Fig. 6

Low-density lipoprotein

10.1158/2767-9764.22551326

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Supplementary Figure S3 from Mitochondrial metabolism drives low-density lipoprotein-induced breast cancer cell migration

Sandrina Nóbrega‐Pereira Francisco Santos Miguel Oliveira Santos Teresa L. Serafim Ana Patrícia Lopes

LDL-induced breast cancer cell migration is mediated by the fatty acid transporter CD36. Related to Fig. 3

CD36

10.1158/2767-9764.22551338.v1

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Supplementary Figure S5 from Mitochondrial metabolism drives low-density lipoprotein-induced breast cancer cell migration

Sandrina Nóbrega‐Pereira Francisco Santos Miguel Oliveira Santos Teresa L. Serafim Ana Patrícia Lopes

LDL-induced migratory behavior of TNBC cells relies on fatty acid transport into the mitochondria. Related to Fig. 5

10.1158/2767-9764.22551332.v1

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

Sandrina Nóbrega‐Pereira Francisco Santos Miguel Oliveira Santos Teresa L. Serafim Ana Patrícia Lopes

Fatty acid profile in relative content (%). Qualitative analysis was calculated by dividing each raw area by the sum of total raw areas. Dash (‘-‘) represents lipid species that were not identified in the sample. Legend: CTR (control), ETO (etomoxir, 100 µM).

Low-density lipoprotein

10.1158/2767-9764.22551317.v1

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Supplementary Figure S7 from Mitochondrial Metabolism Drives Low-density Lipoprotein-induced Breast Cancer Cell Migration

Sandrina Nóbrega‐Pereira Francisco Santos Miguel Oliveira Santos Teresa L. Serafim Ana Patrícia Lopes

¬Reactive oxygen species formation downstream of mitochondria fatty acid entry is required for LDL-induced migration of breast cancer cells. Related to Fig. 6

Low-density lipoprotein

10.1158/2767-9764.22700476.v1

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

Sandrina Nóbrega‐Pereira Francisco Santos Miguel Oliveira Santos Teresa L. Serafim Ana Patrícia Lopes

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

Cell metabolism

10.1158/2767-9764.22592567

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Data from Mitochondrial metabolism drives low-density lipoprotein-induced breast cancer cell migration

Sandrina Nóbrega‐Pereira Francisco Santos Miguel Oliveira Santos Teresa L. Serafim Ana Patrícia Lopes

<div>AbstractMost 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.</div>

CD36

Triple-negative breast cancer

Mitochondrial ROS

10.1158/2767-9764.c.6563219.v2

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Supplementary Figure S3 from Mitochondrial metabolism drives low-density lipoprotein-induced breast cancer cell migration

Sandrina Nóbrega‐Pereira Francisco Santos Miguel Oliveira Santos Teresa L. Serafim Ana Patrícia Lopes

LDL-induced breast cancer cell migration is mediated by the fatty acid transporter CD36. Related to Fig. 3

10.1158/2767-9764.22592564

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