Skip to main content
Key Specialties
Anesthesiology Cardiology Dermatology Diabetology Endocrinology Gastroenterology General Medicine Geriatrics Hematology Infectious Diseases Internal Medicine Nephrology Neurology Obstetrics and Gynecology Oncology Pediatrics Psychiatry Radiology Respiratory Medicine Rheumatology Surgery Urology
Congress Coverage
2024 ESMO Congress 2024 ERS Congress 2024 EASD Congress 2024 ESC Congress 2024 EAN Congress 2024 ASCO Annual Meeting 2024 ACC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on modern management of frailty

LIVE: Thursday 17th October 2024, 18:00-19:30 (CEST)

Frailty has a significant impact on health and wellbeing, especially in older adults. Join our experts to understand the factors that contribute to the development of frailty and find out how to manage the condition and reduce the risk of disability, dependency, and mortality.
ADVANCED SEARCH
Log in
Top
Medical Oncology
Published in:

Open Access 01-10-2024 | Breast Cancer | Review

How mitochondrial dynamics imbalance affects the progression of breast cancer:a mini review

Authors: Jingwen Kuang, Hao Liu, Linlin Feng, Yuan Xue, Huiyi Tang, Pengcheng Xu

Published in: Medical Oncology | Issue 10/2024

Login to get access

Abstract

Despite the high incidence of breast cancer in women worldwide, there are still great challenges in the treatment process. Mitochondria are highly dynamic organelles, and their dynamics involve cellular energy conversion, signal conduction and other processes. In recent years, an increasing number of studies have affirmed the dynamics of mitochondria as the basis for cancer progression and metastasis; that is, an imbalance between mitochondrial fission and fusion may lead to the progression and metastasis of breast cancer. Here, we review the latest insights into mitochondrial dynamics in the progression of breast cancer and emphasize the clinical value of mitochondrial dynamics in diagnosis and prognosis, as well as important advances in clinical research.
Literature
1.
Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17–48.PubMedCrossRef
2.
Trayes KP, Cokenakes SEH. Breast cancer treatment. Am Fam Physician. 2021;104(2):171–8.PubMed
3.
Leung AM, Vu HN, Nguyen KA, Thacker LR, Bear HD. Effects of surgical excision on survival of patients with stage IV breast cancer. J Surg Res. 2010;161(1):83–8.PubMedCrossRef
4.
von Jagow G, Engel WD. Structure and function of the energy-converting system of mitochondria. Angew Chem Int Ed Engl. 1980;19(9):659–75.CrossRef
5.
Szabadkai G, Duchen MR. Mitochondria: the hub of cellular Ca2+ signaling. Physiology (Bethesda). 2008;23:84–94.PubMed
6.
van der Bliek AM, Shen Q, Kawajiri S. Mechanisms of mitochondrial fission and fusion. Cold Spring Harb Perspect Biol. 2013;5(6).
7.
Westermann B. Mitochondrial fusion and fission in cell life and death. Nat Rev Mol Cell Biol. 2010;11(12):872–84.PubMedCrossRef
8.
Maycotte P, Marin-Hernandez A, Goyri-Aguirre M, Anaya-Ruiz M, Reyes-Leyva J, Cortes-Hernandez P. Mitochondrial dynamics and cancer. Tumour Biol. 2017;39(5):1010428317698391.PubMedCrossRef
9.
Itoh K, Nakamura K, Iijima M, Sesaki H. Mitochondrial dynamics in neurodegeneration. Trends Cell Biol. 2013;23(2):64–71.PubMedCrossRef
10.
Xu T, Dong Q, Luo Y, Liu Y, Gao L, Pan Y, et al. Porphyromonas gingivalis infection promotes mitochondrial dysfunction through Drp1-dependent mitochondrial fission in endothelial cells. Int J Oral Sci. 2021;13(1):28.PubMedPubMedCentralCrossRef
11.
Baeuerle PA, Murry JA. Human therapies as a successful liaison between chemistry and biology. Chem Biol. 2014;21(9):1046–54.PubMedCrossRef
12.
Kamerkar SC, Kraus F, Sharpe AJ, Pucadyil TJ, Ryan MT. Dynamin-related protein 1 has membrane constricting and severing abilities sufficient for mitochondrial and peroxisomal fission. Nat Commun. 2018;9(1):5239.PubMedPubMedCentralCrossRef
13.
Kyriakoudi S, Drousiotou A, Petrou PP. When the balance tips: dysregulation of mitochondrial dynamics as a culprit in disease. Int J Mol Sci. 2021;22(9).
14.
Smirnova E, Griparic L, Shurland DL, van der Bliek AM. Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Mol Biol Cell. 2001;12(8):2245–56.PubMedPubMedCentralCrossRef
15.
Miret-Casals L, Sebastian D, Brea J, Rico-Leo EM, Palacin M, Fernandez-Salguero PM, et al. Identification of new activators of mitochondrial fusion reveals a link between mitochondrial morphology and pyrimidine metabolism. Cell Chem Biol. 2018;25(3):268–78 e4.
16.
Yang Z, Wang L, Yang C, Pu S, Guo Z, Wu Q, et al. Mitochondrial membrane remodeling. Front Bioeng Biotechnol. 2021;9: 786806.PubMedCrossRef
17.
Adaniya SM, O-Uchi J, Cypress MW, Kusakari Y, Jhun BS. Posttranslational modifications of mitochondrial fission and fusion proteins in cardiac physiology and pathophysiology. Am J Physiol Cell Physiol. 2019;316(5):C583–604.PubMedPubMedCentralCrossRef
18.
Meeusen S, DeVay R, Block J, Cassidy-Stone A, Wayson S, McCaffery JM, et al. Mitochondrial inner-membrane fusion and crista maintenance requires the dynamin-related GTPase Mgm1. Cell. 2006;127(2):383–95.PubMedCrossRef
19.
Sharma A, Ahmad S, Ahmad T, Ali S, Syed MA. Mitochondrial dynamics and mitophagy in lung disorders. Life Sci. 2021;284: 119876.PubMedCrossRef
20.
Grandemange S, Herzig S, Martinou JC. Mitochondrial dynamics and cancer. Semin Cancer Biol. 2009;19(1):50–6.PubMedCrossRef
21.
Peiris-Pages M, Bonuccelli G, Sotgia F, Lisanti MP. Mitochondrial fission as a driver of stemness in tumor cells: mDIVI1 inhibits mitochondrial function, cell migration and cancer stem cell (CSC) signalling. Oncotarget. 2018;9(17):13254–75.PubMedPubMedCentralCrossRef
22.
23.
Lee YG, Park DH, Chae YC. Role of mitochondrial stress response in cancer progression. Cells. 2022;11(5).
24.
Ghosh P, Vidal C, Dey S, Zhang L. Mitochondria targeting as an effective strategy for cancer therapy. Int J Mol Sci. 2020;21(9).
25.
Eckhardt BL, Cao Y, Redfern AD, Chi LH, Burrows AD, Roslan S, et al. Activation of Canonical BMP4-SMAD7 Signaling Suppresses Breast Cancer Metastasis. Cancer Res. 2020;80(6):1304–15.PubMedCrossRef
26.
27.
Guha M, Avadhani NG. Mitochondrial retrograde signaling at the crossroads of tumor bioenergetics, genetics and epigenetics. Mitochondrion. 2013;13(6):577–91.PubMedCrossRef
28.
Chen L, Zhang J, Lyu Z, Chen Y, Ji X, Cao H, et al. Positive feedback loop between mitochondrial fission and Notch signaling promotes survivin-mediated survival of TNBC cells. Cell Death Dis. 2018;9(11):1050.PubMedPubMedCentralCrossRef
29.
Rehman J, Zhang HJ, Toth PT, Zhang Y, Marsboom G, Hong Z, et al. Inhibition of mitochondrial fission prevents cell cycle progression in lung cancer. FASEB J. 2012;26(5):2175–86.PubMedPubMedCentralCrossRef
30.
Li Y, Chen H, Yang Q, Wan L, Zhao J, Wu Y, et al. Increased Drp1 promotes autophagy and ESCC progression by mtDNA stress mediated cGAS-STING pathway. J Exp Clin Cancer Res. 2022;41(1):76.PubMedPubMedCentralCrossRef
31.
Huang TL, Chang CR, Chien CY, Huang GK, Chen YF, Su LJ, et al. DRP1 contributes to head and neck cancer progression and induces glycolysis through modulated FOXM1/MMP12 axis. Mol Oncol. 2022;16(13):2585–606.PubMedPubMedCentralCrossRef
32.
Liang J, Yang Y, Bai L, Li F, Li E. DRP1 upregulation promotes pancreatic cancer growth and metastasis through increased aerobic glycolysis. J Gastroenterol Hepatol. 2020;35(5):885–95.PubMedCrossRef
33.
Li S, Han S, Zhang Q, Zhu Y, Zhang H, Wang J, et al. FUNDC2 promotes liver tumorigenesis by inhibiting MFN1-mediated mitochondrial fusion. Nat Commun. 2022;13(1):3486.PubMedPubMedCentralCrossRef
34.
Yeon SY, Jo YS, Choi EJ, Kim MS, Yoo NJ, Lee SH. Frameshift mutations in repeat sequences of ANK3, HACD4, TCP10L, TP53BP1, MFN1, LCMT2, RNMT, TRMT6, METTL8 and METTL16 genes in colon cancers. Pathol Oncol Res. 2018;24(3):617–22.PubMedCrossRef
35.
Hu Y, Wang B, Wang L, Wang Z, Jian Z, Deng L. Mammalian STE20-like kinase 1 regulates pancreatic cancer cell survival and migration through Mfn2-mediated mitophagy. Mol Med Rep. 2020;22(1):398–404.PubMedPubMedCentralCrossRef
36.
37.
Pang G, Xie Q, Yao J. Mitofusin 2 inhibits bladder cancer cell proliferation and invasion via the Wnt/beta-catenin pathway. Oncol Lett. 2019;18(3):2434–42.PubMedPubMedCentral
38.
Carmona-Carmona CA, Dalla Pozza E, Ambrosini G, Cisterna B, Palmieri M, Decimo I, et al. Mitochondrial elongation and OPA1 play crucial roles during the stemness acquisition process in pancreatic ductal adenocarcinoma. Cancers (Basel). 2022;14(14).
39.
Wang Y, Li Y, Jiang X, Gu Y, Zheng H, Wang X, et al. OPA1 supports mitochondrial dynamics and immune evasion to CD8(+) T cell in lung adenocarcinoma. PeerJ. 2022;10: e14543.PubMedPubMedCentralCrossRef
40.
Parida PK, Marquez-Palencia M, Ghosh S, Khandelwal N, Kim K, Nair V, et al. Limiting mitochondrial plasticity by targeting DRP1 induces metabolic reprogramming and reduces breast cancer brain metastases. Nat Cancer. 2023;4(6):893–907.PubMedPubMedCentralCrossRef
41.
Si L, Fu J, Liu W, Hayashi T, Nie Y, Mizuno K, et al. Silibinin inhibits migration and invasion of breast cancer MDA-MB-231 cells through induction of mitochondrial fusion. Mol Cell Biochem. 2020;463(1–2):189–201.PubMedCrossRef
42.
Yager JD, Davidson NE. Estrogen carcinogenesis in breast cancer. N Engl J Med. 2006;354(3):270–82.PubMedCrossRef
43.
Sastre-Serra J, Nadal-Serrano M, Pons DG, Roca P, Oliver J. Mitochondrial dynamics is affected by 17beta-estradiol in the MCF-7 breast cancer cell line. Effects on fusion and fission related genes. Int J Biochem Cell Biol. 2012;44(11):1901–5.
44.
Xu R, Jones W, Wilcz-Villega E, Costa AS, Rajeeve V, Bentham RB, et al. The breast cancer oncogene IKKepsilon coordinates mitochondrial function and serine metabolism. EMBO Rep. 2020;21(9): e48260.PubMedPubMedCentralCrossRef
45.
Chen YC, Humphries B, Brien R, Gibbons AE, Chen YT, Qyli T, et al. Functional isolation of tumor-initiating cells using microfluidic-based migration identifies phosphatidylserine decarboxylase as a key regulator. Sci Rep. 2018;8(1):244.PubMedPubMedCentralCrossRef
46.
Humphries BA, Cutter AC, Buschhaus JM, Chen YC, Qyli T, Palagama DSW, et al. Enhanced mitochondrial fission suppresses signaling and metastasis in triple-negative breast cancer. Breast Cancer Res. 2020;22(1):60.PubMedPubMedCentralCrossRef
47.
Chang JC, Chang HS, Yeh CY, Chang HJ, Cheng WL, Lin TT, et al. Regulation of mitochondrial fusion and mitophagy by intra-tumoral delivery of membrane-fused mitochondria or Midiv-1 enhances sensitivity to doxorubicin in triple-negative breast cancer. Biomed Pharmacother. 2022;153: 113484.PubMedCrossRef
48.
Zhao J, Zhang J, Yu M, Xie Y, Huang Y, Wolff DW, et al. Mitochondrial dynamics regulates migration and invasion of breast cancer cells. Oncogene. 2013;32(40):4814–24.PubMedCrossRef
49.
Yamaguchi H, Condeelis J. Regulation of the actin cytoskeleton in cancer cell migration and invasion. Biochim Biophys Acta. 2007;1773(5):642–52.PubMedCrossRef
50.
Xie Y, Wolff DW, Wei T, Wang B, Deng C, Kirui JK, et al. Breast cancer migration and invasion depend on proteasome degradation of regulator of G-protein signaling 4. Cancer Res. 2009;69(14):5743–51.PubMedPubMedCentralCrossRef
51.
Kirui JK, Xie Y, Wolff DW, Jiang H, Abel PW, Tu Y. Gbetagamma signaling promotes breast cancer cell migration and invasion. J Pharmacol Exp Ther. 2010;333(2):393–403.PubMedPubMedCentralCrossRef
52.
Fan WP, Du XN, Zhuang Y, Zhao XF, Sun HY, Zhang H. Expression and clinical significance of mitochondrial fission regulator 1 in breast invasive carcinoma analysed by high - throughput and multi -omics data. J Mod Oncol. 2019;27(12):2101–5. (in Chinece)
53.
Lu G, Lai Y, Wang T, Lin W, Lu J, Ma Y, et al. Mitochondrial fission regulator 2 (MTFR2) promotes growth, migration, invasion and tumour progression in breast cancer cells. Aging (Albany NY). 2019;11(22):10203–19.PubMedCrossRef
54.
Reedijk M, Odorcic S, Chang L, Zhang H, Miller N, McCready DR, et al. High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival. Cancer Res. 2005;65(18):8530–7.PubMedCrossRef
55.
Song C, Zhang J, Xu C, Gao M, Li N, Geng Q. The critical role of gamma-secretase and its inhibitors in cancer and cancer therapeutics. Int J Biol Sci. 2023;19(16):5089–103.PubMedPubMedCentralCrossRef
56.
Chang JC, Chang HS, Wu YC, Cheng WL, Lin TT, Chang HJ, et al. Mitochondrial transplantation regulates antitumour activity, chemoresistance and mitochondrial dynamics in breast cancer. J Exp Clin Cancer Res. 2019;38(1):30.PubMedPubMedCentralCrossRef
57.
Yi L, Shang XJ, Lv L, Wang Y, Zhang J, Quan C, et al. Cadmium-induced apoptosis of Leydig cells is mediated by excessive mitochondrial fission and inhibition of mitophagy. Cell Death Dis. 2022;13(11):928.PubMedPubMedCentralCrossRef
58.
59.
60.
Li T, Han J, Jia L, Hu X, Chen L, Wang Y. PKM2 coordinates glycolysis with mitochondrial fusion and oxidative phosphorylation. Protein Cell. 2019;10(8):583–94.PubMedPubMedCentralCrossRef
61.
Zamberlan M, Boeckx A, Muller F, Vinelli F, Ek O, Vianello C, et al. Inhibition of the mitochondrial protein Opa1 curtails breast cancer growth. J Exp Clin Cancer Res. 2022;41(1):95.PubMedPubMedCentralCrossRef
62.
Weiner-Gorzel K, Murphy M. Mitochondrial dynamics, a new therapeutic target for triple negative breast cancer. Biochim Biophys Acta Rev Cancer. 2021;1875(2): 188518.PubMedCrossRef
63.
Lucantoni F, Dussmann H, Prehn JHM. Metabolic Targeting of breast cancer cells with the 2-Deoxy-D-Glucose and the mitochondrial bioenergetics inhibitor MDIVI-1. Front Cell Dev Biol. 2018;6:113.PubMedPubMedCentralCrossRef
64.
Chang JC, Chang HS, Wu YC, Cheng WL, Lin TT, Chang HJ, et al. Antitumor actions of intratumoral delivery of membrane-fused mitochondria in a mouse model of triple-negative breast cancers. Onco Targets Ther. 2020;13:5241–55.PubMedPubMedCentralCrossRef
65.
Kumar B, Koul S, Khandrika L, Meacham RB, Koul HK. Oxidative stress is inherent in prostate cancer cells and is required for aggressive phenotype. Cancer Res. 2008;68(6):1777–85.PubMedCrossRef
66.
Li L, Yu AQ. The functional role of peroxiredoxin 3 in reactive oxygen species, apoptosis, and chemoresistance of cancer cells. J Cancer Res Clin Oncol. 2015;141(12):2071–7.PubMedCrossRef
67.
Kropotov A, Gogvadze V, Shupliakov O, Tomilin N, Serikov VB, Tomilin NV, et al. Peroxiredoxin V is essential for protection against apoptosis in human lung carcinoma cells. Exp Cell Res. 2006;312(15):2806–15.PubMedCrossRef
68.
Chen J, Cao X, Qin X, Liu H, Chen S, Zhong S, et al. Proteomic analysis of the molecular mechanism of curcumin/beta-cyclodextrin polymer inclusion complex inhibiting HepG2 cells growth. J Food Biochem. 2020;44(2): e13119.PubMedCrossRef
69.
Lv C, Huang Y, Wang Q, Wang C, Hu H, Zhang H, et al. Ainsliadimer A induces ROS-mediated apoptosis in colorectal cancer cells via directly targeting peroxiredoxin 1 and 2. Cell Chem Biol. 2023;30(3):295–307 e5.
70.
Liu A, Li Y, Lu S, Cai C, Zou F, Meng X. Stanniocalcin 1 promotes lung metastasis of breast cancer by enhancing EGFR-ERK-S100A4 signaling. Cell Death Dis. 2023;14(7):395.PubMedPubMedCentralCrossRef
71.
Huang T, Meng F, Huang H, Wang L, Wang L, Liu Y, et al. GALNT8 suppresses breast cancer cell metastasis potential by regulating EGFR O-GalNAcylation. Biochem Biophys Res Commun. 2022;601:16–23.PubMedCrossRef
72.
Li ED, Lin Q, Meng YQ, Zhang LY, Song PP, Li N, et al. 2,4-Disubstituted quinazolines targeting breast cancer cells via EGFR-PI3K. Eur J Med Chem. 2019;172:36–47.PubMedCrossRef
73.
74.
Zhang J, Fan M, Jin C, Wang Z, Yao Y, Shi Y, et al. NFIC1 suppresses migration and invasion of breast cancer cells through interferon-mediated Jak-STAT pathway. Arch Biochem Biophys. 2022;727: 109346.PubMedCrossRef
75.
Hosford SR, Miller TW. Clinical potential of novel therapeutic targets in breast cancer: CDK4/6, Src, JAK/STAT, PARP, HDAC, and PI3K/AKT/mTOR pathways. Pharmgenomics Pers Med. 2014;7:203–15.PubMedPubMedCentral
76.
Ismail T, Kim Y, Lee H, Lee DS, Lee HS. Interplay between mitochondrial peroxiredoxins and ROS in cancer development and progression. Int J Mol Sci. 2019;20(18).
77.
Jia H, Wang Z, Zhang J, Feng F. gamma-Secretase inhibitors for breast cancer and hepatocellular carcinoma: from mechanism to treatment. Life Sci. 2021;268: 119007.PubMedCrossRef
Metadata
Title
How mitochondrial dynamics imbalance affects the progression of breast cancer:a mini review
Authors
Jingwen Kuang
Hao Liu
Linlin Feng
Yuan Xue
Huiyi Tang
Pengcheng Xu
Publication date
01-10-2024
Publisher
Springer US
Published in
Medical Oncology / Issue 10/2024
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-024-02479-2

Other articles of this Issue 10/2024

Medical Oncology 10/2024 Go to the issue

Review Article

The Sirt1/Nrf2 pathway is a key factor for drug therapy in chemotherapy-induced cardiotoxicity: a Mini-Review

Comment

Letter to the editor: comment on “Chitosan-loaded piperlongumine nanoparticles and kaempferol enhance the anti-cancer action of doxorubicin in targeting of Ehrlich solid adenocarcinoma: in vivo and in silico modeling study”

Letter to the Editor

Comment on “gemcitabine, PI3kinase-Akt pathway inhibition and radiation in human glioma cell lines” by M.S. Elnaggar et al.1

Review Article

The treatment landscape of triple-negative breast cancer

Review

Current diagnostic and quantitative techniques in the field of lymphedema management: a critical review

Review

The role of IL-22 in cancer

EASD 2024

‘Noninferior’ reduction of type 1 diabetes HbA1c by weekly insulin efsitora alfa

Weekly treatment with insulin efsitora is noninferior to daily insulin degludec for the reduction of HbA1c in adults with type 1 diabetes, show the findings of the QWINT-5 trial.

Read more

Weight loss with new obesity drug amycretin

Tirzepatide significantly reduces UACR in individuals with obesity and type 2 diabetes

Liraglutide reduces BMI for young children with obesity

» View more highlights on the EASD 2024 hub page

2024 ESC Congress

Noise pollution dangerous for heart health

Two studies underscore the adverse impact of noise pollution on the risk for and prognosis after myocardial infarction.

Read more

Post-TAVI follow up: deploying virtual assistants

Antihypertensives: more effective at morning or night?

Low Lp(a) levels unlikely to increase the risk of diabetes

» View more highlights on the 2024 ESC Congress hub page

A quick guide to ECGs

Improve your ECG interpretation skills with this comprehensive, rapid, interactive course. Expert advice provides detailed feedback as you work through 50 ECGs covering the most common cardiac presentations to ensure your practice stays up to date. 

PD Dr. Carsten W. Israel
Developed by: Springer Medizin
Start the cases

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Read more
Image Credits