Mitochondrial genotype and breast cancer predisposition

Czarnecka, Anna; Krawczyk, Tomasz; Plak, Katarzyna; Klemba, Aleksandra; Zdrozny, Marek; Arnold, Rebecca S.; Kofler, Barbara; Golik, Paweł; Szybińska, Aleksandra; Lubiński, Jan; Mossakowska, Małgorzata; Bartnik, Ewa; Petros, John A.

doi:10.3892/or_00001014

Cited by 14 publications

(1 citation statement)

References 76 publications

(121 reference statements)

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“…Tommasi S et al, reported that the H haplogroup was associated with breast cancer tumor grade differentiation and with BRCA2 mutations [ 23 ], suggesting that mtDNA variants may act as a genetic modifier for breast cancer. While the mtDNA U haplogroup has been overrepresented in control subjects [ 24 ], the mtDNA I haplogroup has higher association with the breast cancer group [ 25 ], although there is still some controversy of the association between European mtDNA haplogroups and breast cancer risk [ 26 ]. Multiple studies have speculated that in Asian, African-American, and European-American populations, there may be an increased association between the m.10398G > A polymorphism and breast cancer [ 27 , 28 , 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Altered Retrograde Signaling Patterns in Breast Cancer Cells Cybrids with H and J Mitochondrial DNA Haplogroups

Chang

Singh

Thaker

et al. 2022

IJMS

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The aim of this study was to determine the role of retrograde signaling (mitochondria to nucleus) in MCF7 breast cancer cells. Therefore, in the present study, MCF7-H and MCF7-J cybrids were produced using the mitochondria from the same H and J individuals that were already used in our non-diseased retinal pigment epithelium (ARPE19) cybrids. MCF7 cybrids were treated with cisplatin and analyzed for cell viability, mitochondrial membrane potential, ROS, and expression levels of genes associated with the cGAS-STING and cancer-related pathways. Results showed that unlike the ARPE19-H and ARPE19-J cybrids, the untreated MCF7-H and MCF7-J cybrids had similar levels of ATP, lactate, and OCR: ECAR ratios. After cisplatin treatment, MCF7-H and MCF7-J cybrids showed similar (a) decreases in cell viability and ROS levels; (b) upregulation of ABCC1, BRCA1 and CDKN1A/P21; and (c) downregulation of EGFR. Cisplatin-treated ARPE19-H and ARPE19-J cybrids showed increased expression of six cGAS-STING pathway genes, while two were increased for MCF7-J cybrids. In summary, the ARPE19-H and ARPE19-J cybrids behave differentially from each other with or without cisplatin. In contrast, the MCF7-H and MCF7-J cybrids had identical metabolic/bioenergetic profiles and cisplatin responses. Our findings suggest that cancer cell nuclei might have a diminished ability to respond to the modulating signaling of the mtDNA that occurs via the cGAS-STING pathway.

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Section: Discussionmentioning

confidence: 99%

Altered Retrograde Signaling Patterns in Breast Cancer Cells Cybrids with H and J Mitochondrial DNA Haplogroups

Chang

Singh

Thaker

et al. 2022

IJMS

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Oncogenic metabolic reprogramming in breast cancer: focus on signaling pathways and mitochondrial genes

Malayil,

Chhichholiya,

Vasudeva

et al. 2023

Med Oncol

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Mitochondrial determinants of cancer health disparities

Choudhury

Singh

2017

Seminars in Cancer Biology

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Mitochondria are involved in the generation of energy, cell growth and differentiation, cellular signaling, cell cycle control, and cell death. To date, the mitochondrial basis of cancer disparities is unknown. The goal of this review is to provide an understanding and a framework of mitochondrial determinants that may contribute to cancer disparities in racially different populations. Mitochondria, which are multi-functional, have been implicated in the initiation and progression of cancers in relation to metabolic alterations in transformed cells. Due to ethnic-based diversity, the mitochondrial genome (mtDNA) could be a basis for inherited racial disparities and for acquired somatic mutations during tumorigenesis. In African Americans, several germline, population-specific haplotype variants in mtDNA as well as depletion of mtDNA have been linked to cancer predisposition and cancer disparities. Indeed, depletion of mtDNA and mutations in mtDNA or nuclear genome (nDNA)-encoded mitochondrial proteins lead to mitochondrial dysfunction and promote resistance to apoptosis, the epithelial-to-mesenchymal transition, and metastatic disease, which in turn can contribute to cancer disparity and tumor aggressiveness related to racial disparities. Ethnic differences at the level of expression or genetic variations in nDNA encoding the mitochondrial proteome, including mitochondria-localized mtDNA replication and repair proteins, miRNA, transcription factors, kinases and phosphatases, and tumor suppressors and oncogenes may underlie susceptibility to high-risk and aggressive cancers found in African Americans and other ethnicities. The mitochondrial retrograde signaling that alters the expression profile of nuclear genes in response to dysfunctional mitochondria is a mechanism for tumorigenesis. In ethnic populations, differences in mitochondrial function may alter the cross talk between mitochondria and the nucleus at epigenetic and genetic levels, which can also contribute to cancer health disparities. Targeting mitochondrial determinants and mitochondrial retrograde signaling could provide a promising strategy for the development of selective anticancer therapy for dealing with cancer disparities. Further, agents that restore mitochondrial function to optimal levels should permit sensitivity to anticancer agents for the treatment of aggressive tumors that occur in racially diverse populations and hence help in reducing racial disparities.

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Mitochondrial genotype and breast cancer predisposition

Cited by 14 publications

References 76 publications

Altered Retrograde Signaling Patterns in Breast Cancer Cells Cybrids with H and J Mitochondrial DNA Haplogroups

Altered Retrograde Signaling Patterns in Breast Cancer Cells Cybrids with H and J Mitochondrial DNA Haplogroups

Oncogenic metabolic reprogramming in breast cancer: focus on signaling pathways and mitochondrial genes

Mitochondrial determinants of cancer health disparities

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