Exploration of Medicine

Table 1. Summary of the discussed metastatic processes of breast cancer affected by various transcription factors

Transcription factor	Metastatic process affected
Transcription factor	Angiogenesis/Vascularization	EMT/MET	Migration	Invasion	Cell cycle/Apoptosis
E2F	√			√	√
HIF	√	√		√
EMT master regulators		√	√	√	√
SOX	√	√	√	√
ETS	√	√	√	√	√
YY1	√
FoxM1		√	√	√
Bach1	√		√	√
SIX	√	√
RUNX				√
MYC	√				√
KLFs		√	√	√	√
c-Jun			√		√

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EMT: epithelial-mesenchymal transition; MET: mesenchymal-epithelial transition; HIF: hypoxia-inducible factor; SOX: sex determining region Y-related high-mobility group box; ETS: E26 transformation-specific; YY1: Yin Yang 1; FoxM1: forkhead box M1; Bach1: BTB domain and CNC homology 1; SIX: sineoculis homeobox homolog; MYC: myelocytomatosis; KLFs: Kruppel-like factors; RUNX: runt-related transcription factor

Declarations

Author contributions

SM: Conceptualization, Investigation, Visualization, Writing—original draft, Writing—review & editing. CM: Conceptualization, Funding acquisition, Supervision. YL: Project administration, Validation, Supervision. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that there are no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

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Consent to publication

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Availability of data and materials

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Funding

This paper was funded by The Assisi Foundation of Memphis, Brown, Chester, PhD (PI). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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References

Park M, Kim D, Ko S, Kim A, Mo K, Yoon H. Breast Cancer Metastasis: Mechanisms and Therapeutic Implications. Int J Mol Sci. 2022;23:6806. [DOI] [PubMed] [PMC]

Johnson J, Thijssen B, McDermott U, Garnett M, Wessels LF, Bernards R. Targeting the RB-E2F pathway in breast cancer. Oncogene. 2016;35:4829–35. [DOI] [PubMed] [PMC]

Hollern DP, Honeysett J, Cardiff RD, Andrechek ER. The E2F transcription factors regulate tumor development and metastasis in a mouse model of metastatic breast cancer. Mol Cell Biol. 2014;34:3229–43. [DOI] [PubMed] [PMC]

Liu ZL, Bi XW, Liu PP, Lei DX, Wang Y, Li ZM, et al. Expressions and prognostic values of the E2F transcription factors in human breast carcinoma. Cancer Manag Res. 2018;10:3521–32. [DOI] [PubMed] [PMC]

Song L, Li H, Ma RR, Liu S, Zhang GH, Guo XY, et al. E2F1-initiated transcription of PRSS22 promotes breast cancer metastasis by cleaving ANXA1 and activating FPR2/ERK signaling pathway. Cell Death Dis. 2022;13:982. [DOI] [PubMed] [PMC]

Gilkes DM, Semenza GL. Role of hypoxia-inducible factors in breast cancer metastasis. Future Oncol. 2013;9:1623–36. [DOI] [PubMed] [PMC]

de Heer EC, Jalving M, Harris AL. HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer. J Clin Invest. 2020;130:5074–87. [DOI] [PubMed] [PMC]

Graham AM, Presnell JS. Hypoxia Inducible Factor (HIF) transcription factor family expansion, diversification, divergence and selection in eukaryotes. PLoS One. 2017;12:e0179545. [DOI] [PubMed] [PMC]

Liao D, Corle C, Seagroves TN, Johnson RS. Hypoxia-inducible factor-1α is a key regulator of metastasis in a transgenic model of cancer initiation and progression. Cancer Res. 2007;67:563–72. [DOI] [PubMed]

10.

Hegde M, Daimary UD, Kumar A, Chinnathambi A, Alharbi SA, Shakibaei M, et al. STAT3/HIF1A and EMT specific transcription factors regulated genes: Novel predictors of breast cancer metastasis. Gene. 2022;818:146245. [DOI] [PubMed]

11.

Ell B, Kang Y. Transcriptional control of cancer metastasis. Trends Cell Biol. 2013;23:603–11. [DOI] [PubMed] [PMC]

12.

Liu ZJ, Semenza GL, Zhang HF. Hypoxia-inducible factor 1 and breast cancer metastasis. J Zhejiang Univ Sci B. 2015;16:32–43. [DOI] [PubMed] [PMC]

13.

Wu HT, Zhong HT, Li GW, Shen JX, Ye QQ, Zhang ML, et al. Oncogenic functions of the EMT-related transcription factor ZEB1 in breast cancer. J Transl Med. 2020;18:51. [DOI] [PubMed] [PMC]

14.

Addison JB, Voronkova MA, Fugett JH, Lin CC, Linville NC, Trinh B, et al. Functional Hierarchy and Cooperation of EMT Master Transcription Factors in Breast Cancer Metastasis. Mol Cancer Res. 2021;19:784–98. [DOI] [PubMed] [PMC]

15.

Zhang P, Sun Y, Ma L. ZEB1: at the crossroads of epithelial-mesenchymal transition, metastasis and therapy resistance. Cell Cycle. 2015;14:481–7. [DOI] [PubMed] [PMC]

16.

Tsai JH, Yang J. Epithelial–mesenchymal plasticity in carcinoma metastasis. Genes Dev. 2013;27:2192–206. [DOI] [PubMed] [PMC]

17.

Tang H, Massi D, Hemmings BA, Mandalà M, Hu Z, Wicki A, et al. AKT-ions with a TWIST between EMT and MET. Oncotarget. 2016;7:62767–77. [DOI] [PubMed] [PMC]

18.

de Herreros AG, Peiró S, Nassour M, Savagner P. Snail family regulation and epithelial mesenchymal transitions in breast cancer progression. J Mammary Gland Biol Neoplasia. 2010;15:135–47. [DOI] [PubMed] [PMC]

19.

Liu Q, Guan C, Liu C, Li H, Wu J, Sun C. Targeting hypoxia-inducible factor-1alpha: A new strategy for triple-negative breast cancer therapy. Biomed Pharmacother. 2022;156:113861. [DOI] [PubMed]

20.

Antón-García P, Haghighi EB, Rose K, Vladimirov G, Boerries M, Hecht A. TGFβ1-Induced EMT in the MCF10A Mammary Epithelial Cell Line Model Is Executed Independently of SNAIL1 and ZEB1 but Relies on JUNB-Coordinated Transcriptional Regulation. Cancers (Basel). 2023;15:558. [DOI] [PubMed] [PMC]

21.

Grimm D, Bauer J, Wise P, Krüger M, Simonsen U, Wehland M, et al. The role of SOX family members in solid tumours and metastasis. Semin Cancer Biol. 2020;67:122–53. [DOI] [PubMed]

22.

Liu Y, Guo W. SOX factors as cell-state regulators in the mammary gland and breast cancer. Semin Cell Dev Biol. 2021;114:126–33. [DOI] [PubMed] [PMC]

23.

Mehta GA, Khanna P, Gatza ML. Emerging Role of SOX Proteins in Breast Cancer Development and Maintenance. J Mammary Gland Biol Neoplasia. 2019;24:213–30. [DOI] [PubMed] [PMC]

24.

Kar A, Gutierrez-Hartmann A. Molecular mechanisms of ETS transcription factor-mediated tumorigenesis. Crit Rev Biochem Mol Biol. 2013;48:522–43. [DOI] [PubMed] [PMC]

25.

de Launoit Y, Chotteau-Lelievre A, Beaudoin C, Coutte L, Netzer S, Brenner C, et al. The PEA3 Group of ETS-related Transcription Factors. In: Mol JA, Clegg RA, editors. Biology of the Mammary Gland. Boston, MA: Springer US; 2002. pp. 107–16. [DOI] [PubMed]

26.

Sun Y, Zhang H, Ma R, Guo X, Zhang G, Liu S, et al. ETS-1-activated LINC01016 over-expression promotes tumor progression via suppression of RFFL-mediated DHX9 ubiquitination degradation in breast cancers. Cell Death Dis. 2023;14:507. [DOI] [PubMed] [PMC]

27.

Kaufhold S, Garbán H, Bonavida B. Yin Yang 1 is associated with cancer stem cell transcription factors (SOX2, OCT4, BMI1) and clinical implication. J Exp Clin Cancer Res. 2016;35:84. [DOI] [PubMed] [PMC]

28.

Guo Q, Wang T, Yang Y, Gao L, Zhao Q, Zhang W, et al. Transcriptional Factor Yin Yang 1 Promotes the Stemness of Breast Cancer Cells by Suppressing miR-873-5p Transcriptional Activity. Mol Ther Nucleic Acids. 2020;21:527–41. [DOI] [PubMed] [PMC]

29.

Saba R, Alsayed A, Zacny JP, Dudek AZ. The Role of Forkhead Box Protein M1 in Breast Cancer Progression and Resistance to Therapy. Int J Breast Cancer. 2016;2016:9768183. [DOI] [PubMed] [PMC]

30.

Zhang YL, Ma Y, Zeng YQ, Liu Y, He EP, Liu YT, et al. A narrative review of research progress on FoxM1 in breast cancer carcinogenesis and therapeutics. Ann Transl Med. 2021;9:1704. [DOI] [PubMed] [PMC]

31.

O’Regan RM, Nahta R. Targeting forkhead box M1 transcription factor in breast cancer. Biochem Pharmacol. 2018;154:407–13. [DOI] [PubMed] [PMC]

32.

Lambert M, Jambon S, Depauw S, David-Cordonnier MH. Targeting Transcription Factors for Cancer Treatment. Molecules. 2018;23:1479. [DOI] [PubMed] [PMC]

33.

Padilla J, Lee J. A Novel Therapeutic Target, BACH1, Regulates Cancer Metabolism. Cells. 2021;10:634. [DOI] [PubMed] [PMC]

34.

Liang Y, Wu H, Lei R, Chong RA, Wei Y, Lu X, et al. Transcriptional network analysis identifies BACH1 as a master regulator of breast cancer bone metastasis. J Biol Chem. 2012;287:33533–44. [DOI] [PubMed] [PMC]

35.

Xu HX, Wu KJ, Tian YJ, Liu Q, Han N, He XL, et al. Expression profile of SIX family members correlates with clinic-pathological features and prognosis of breast cancer: A systematic review and meta-analysis. Medicine (Baltimore). 2016;95:e4085. [DOI] [PubMed] [PMC]

36.

Blevins MA, Towers CG, Patrick AN, Zhao R, Ford HL. The SIX1-EYA transcriptional complex as a therapeutic target in cancer. Expert Opin Ther Targets. 2015;19:213–25. [DOI] [PubMed] [PMC]

37.

Chimge NO, Frenkel B. The RUNX family in breast cancer: relationships with estrogen signaling. Oncogene. 2013;32:2121–30. [DOI] [PubMed] [PMC]

38.

Wysokinski D, Blasiak J, Pawlowska E. Role of RUNX2 in Breast Carcinogenesis. Int J Mol Sci. 2015;16:20969–93. [DOI] [PubMed] [PMC]

39.

Duffy MJ, O’Grady S, Tang M, Crown J. MYC as a target for cancer treatment. Cancer Treat Rev. 2021;94:102154. [DOI] [PubMed]

40.

Wang L, Zhang S, Wang X. The Metabolic Mechanisms of Breast Cancer Metastasis. Front Oncol. 2021;10:602416. [DOI] [PubMed] [PMC]

41.

Zhang J, Li G, Feng L, Lu H, Wang X. Krüppel-like factors in breast cancer: Function, regulation and clinical relevance. Biomed Pharmacother. 2020;123:109778. [DOI] [PubMed]

42.

Bai X, Jiang X, Liu Y, Wang Y, Jiang X, Song G, et al. Krüppel-like factor 9 upregulates E-cadherin transcription and represses breast cancer invasion and metastasis. Am J Cancer Res. 2021;11:3660–73. [PubMed] [PMC]

43.

Bang S, Li J, Zhang M, Cui R, Wu X, Xin Z, et al. The Clinical Relevance and Function of Krüppel-Like Factor 16 in Breast Cancer. Cancer Manag Res. 2020;12:6373–83. [DOI] [PubMed] [PMC]

44.

Lin L, Pfender K, Ditsch N, Kuhn C, Rahmeh M, Peng L, et al. KLF11 is an independent negative prognostic factor for breast cancer from a cohort study and induces proliferation and inhibits apoptosis in vitro. Breast Cancer. 2023;30:758–71. [DOI] [PubMed] [PMC]

45.

Shao W, Li S, Li L, Lin K, Liu X, Wang H, et al. Chemical genomics reveals inhibition of breast cancer lung metastasis by Ponatinib via c-Jun. Protein Cell. 2019;10:161–77. [DOI] [PubMed] [PMC]

46.

Zhu P, Liu G, Wang X, Lu J, Zhou Y, Chen S, et al. Transcription factor c-Jun modulates GLUT1 in glycolysis and breast cancer metastasis. BMC Cancer. 2022;22:1283. [DOI] [PubMed] [PMC]

47.

Jiang C, Zhu Y, Chen H, Lin J, Xie R, Li W, et al. Targeting c-Jun inhibits fatty acid oxidation to overcome tamoxifen resistance in estrogen receptor-positive breast cancer. Cell Death Dis. 2023;14:653. [DOI] [PubMed] [PMC]

48.

Chang JC. Cancer stem cells: Role in tumor growth, recurrence, metastasis, and treatment resistance. Medicine (Baltimore). 2016;95:S20–5. [DOI] [PubMed] [PMC]

49.

Madu CO, Wang S, Madu CO, Lu Y. Angiogenesis in Breast Cancer Progression, Diagnosis, and Treatment. J Cancer. 2020;11:4474–94. [DOI] [PubMed] [PMC]

50.

Wang Y, Zhou BP. Epithelial-mesenchymal transition in breast cancer progression and metastasis. Chin J Cancer. 2011;30:603–11. [DOI] [PubMed] [PMC]

51.

Takebe N, Warren RQ, Ivy SP. Breast cancer growth and metastasis: interplay between cancer stem cells, embryonic signaling pathways and epithelial-to-mesenchymal transition. Breast Cancer Res. 2011;13:211. [DOI] [PubMed] [PMC]

52.

Bushweller JH. Targeting transcription factors in cancer — from undruggable to reality. Nat Rev Cancer. 2019;19:611–24. [DOI] [PubMed] [PMC]

53.

Gilkes DM. Implications of Hypoxia in Breast Cancer Metastasis to Bone. Int J Mol Sci. 2016;17:1669. [DOI] [PubMed] [PMC]

54.

da Silveira WA, Palma PVB, Sicchieri RD, Villacis RAR, Mandarano LRM, Oliveira TMG, et al. Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype. Sci Rep. 2017;7:2851. [DOI] [PubMed] [PMC]

55.

Demirkan B. The Roles of Epithelial-to-Mesenchymal Transition (EMT) and Mesenchymal-to-Epithelial Transition (MET) in Breast Cancer Bone Metastasis: Potential Targets for Prevention and Treatment. J Clin Med. 2013;2:264–82. [DOI] [PubMed] [PMC]