RUNX3 exerts tumor-suppressive role through inhibiting EXOSC4 expression.
Core Binding Factor Alpha 3 Subunit
/ genetics
Humans
Breast Neoplasms
/ genetics
Female
Promoter Regions, Genetic
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Aldehyde Dehydrogenase 1 Family
/ metabolism
SOXB1 Transcription Factors
/ metabolism
Retinal Dehydrogenase
/ metabolism
Neoplastic Stem Cells
/ metabolism
Breast cancer
Cancer stem cells
EXOSC4
Estrogen receptor
RUNX3
Journal
Functional & integrative genomics
ISSN: 1438-7948
Titre abrégé: Funct Integr Genomics
Pays: Germany
ID NLM: 100939343
Informations de publication
Date de publication:
17 May 2024
17 May 2024
Historique:
received:
24
02
2024
accepted:
01
05
2024
revised:
23
04
2024
medline:
24
6
2024
pubmed:
24
6
2024
entrez:
24
6
2024
Statut:
epublish
Résumé
Breast cancer severely affects women health. 70% of breast cancer are estrogen receptor positive. Breast cancer stem cells are a group of tumor with plasticity, causing tumor relapse and metastasis. RUNX3 is a tumor suppressor frequently inactivated in estrogen receptor positive breast cancer. However, the mechanism of how RUNX3 is involved in the regualation of cancer stem cell traits in estrogen receptor positive breast cancer remains elusive. In this study, we utilized cut-tag assay to investigate the binding profile RUNX3 in BT474 and T47D cell, and confirmed EXOSC4 as the bona-fide target of RUNX3; RUNX3 could bind to the promoter are of EXOSC4 to suppress its expression. Furthermore, EXOSC4 could increase the colony formation, cell invasion and mammosphere formation ability of breast cancer cells and upregulate the the expression of SOX2 and ALDH1. Consistent with these findings, EXOSC4 was associated with poorer survival for Luminal B/Her2 breast cancer patiens. At last, we confirmed that EXOSC4 mediated the tumor suppressive role of RUNX3 in breast cancer cells. In conclusion, we demonstrate that RUNX3 directly binds to the promoter region of EXOSC4, leading to the suppression of EXOSC4 expression and exerting a tumor-suppressive effect in estrogen receptor postivive breast cancer cells.
Identifiants
pubmed: 38913281
doi: 10.1007/s10142-024-01363-6
pii: 10.1007/s10142-024-01363-6
doi:
Substances chimiques
Core Binding Factor Alpha 3 Subunit
0
Runx3 protein, human
0
Aldehyde Dehydrogenase 1 Family
EC 1.2.1
SOXB1 Transcription Factors
0
ALDH1A1 protein, human
EC 1.2.1.36
Retinal Dehydrogenase
EC 1.2.1.36
SOX2 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
103Subventions
Organisme : National Natural Science Foundation of China
ID : No. 82003165
Organisme : National Natural Science Foundation of China
ID : No. 82003165
Organisme : National Natural Science Foundation of China
ID : No. 82003165
Organisme : National Natural Science Foundation of China
ID : No. 82003165
Organisme : National Natural Science Foundation of China
ID : No. 82003165
Organisme : National Natural Science Foundation of China
ID : No. 82003165
Organisme : National Natural Science Foundation of China
ID : No. 82003165
Organisme : National Natural Science Foundation of China
ID : No. 82003165
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100(7):3983–3988. https://doi.org/10.1073/pnas.0530291100
doi: 10.1073/pnas.0530291100
pubmed: 12629218
pmcid: 153034
Britigan EMC, Wan J, Sam DK, Copeland SE, Lasek AL, Hrycyniak LCF, Wang L, Audhya A, Burkard ME, Roopra A et al (2022) Increased Aurora B expression reduces substrate phosphorylation and induces chromosomal instability. Front Cell Dev Biol 10:1018161. https://doi.org/10.3389/fcell.2022.1018161
doi: 10.3389/fcell.2022.1018161
pubmed: 36313574
pmcid: 9606593
Brouwer R, Allmang C, Raijmakers R, van Aarssen Y, Egberts WV, Petfalski E, van Venrooij WJ, Tollervey D, Pruijn GJ (2001) Three novel components of the human exosome. J Biol Chem 276(9):6177–6184. https://doi.org/10.1074/jbc.M007603200
doi: 10.1074/jbc.M007603200
pubmed: 11110791
Chen LF (2012) Tumor suppressor function of RUNX3 in breast cancer. J Cell Biochem 113(5):1470–1477. https://doi.org/10.1002/jcb.24074
doi: 10.1002/jcb.24074
pubmed: 22275124
pmcid: 3337355
Chimge NO, Little GH, Baniwal SK, Adisetiyo H, Xie Y, Zhang T, O’Laughlin A, Liu ZY, Ulrich P, Martin A et al (2016) RUNX1 prevents oestrogen-mediated AXIN1 suppression and β-catenin activation in ER-positive breast cancer. Nat Commun 7:10751. https://doi.org/10.1038/ncomms10751
doi: 10.1038/ncomms10751
pubmed: 26916619
pmcid: 4773428
Cordenonsi M, Zanconato F, Azzolin L, Forcato M, Rosato A, Frasson C, Inui M, Montagner M, Parenti AR, Poletti A et al (2011) The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell 147(4):759–772. https://doi.org/10.1016/j.cell.2011.09.048
doi: 10.1016/j.cell.2011.09.048
pubmed: 22078877
Cui K, Gong L, Zhang H, Chen Y, Liu B, Gong Z, Li J, Wang Y, Sun S, Li Y et al (2022) EXOSC8 promotes colorectal cancer tumorigenesis via regulating ribosome biogenesis-related processes. Oncogene 41(50):5397–5410. https://doi.org/10.1038/s41388-022-02530-4
doi: 10.1038/s41388-022-02530-4
pubmed: 36348012
DeSantis CE, Ma J, Gaudet MM, Newman LA, Miller KD, Goding Sauer A, Jemal A, Siegel RL (2019) Breast cancer statistics, 2019. CA Cancer J Clin 69(6):438–451. https://doi.org/10.3322/caac.21583
doi: 10.3322/caac.21583
pubmed: 31577379
Fritz AJ, Hong D, Boyd J, Kost J, Finstaad KH, Fitzgerald MP, Hanna S, Abuarqoub AH, Malik M, Bushweller J et al (2020) RUNX1 and RUNX2 transcription factors function in opposing roles to regulate breast cancer stem cells. J Cell Physiol 235(10):7261–7272. https://doi.org/10.1002/jcp.29625
doi: 10.1002/jcp.29625
pubmed: 32180230
pmcid: 7415511
Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S et al (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1(5):555–567. https://doi.org/10.1016/j.stem.2007.08.014
doi: 10.1016/j.stem.2007.08.014
pubmed: 18371393
pmcid: 2423808
Gupta PB, Pastushenko I, Skibinski A, Blanpain C, Kuperwasser C (2019) Phenotypic plasticity: driver of cancer initiation, progression, and therapy resistance. Cell Stem Cell 24(1):65–78. https://doi.org/10.1016/j.stem.2018.11.011
doi: 10.1016/j.stem.2018.11.011
pubmed: 30554963
Huang B, Qu Z, Ong CW, Tsang YH, Xiao G, Shapiro D, Salto-Tellez M, Ito K, Ito Y, Chen LF (2012) RUNX3 acts as a tumor suppressor in breast cancer by targeting estrogen receptor α. Oncogene 31(4):527–534. https://doi.org/10.1038/onc.2011.252
doi: 10.1038/onc.2011.252
pubmed: 21706051
Jeselsohn R, Cornwell M, Pun M, Buchwalter G, Nguyen M, Bango C, Huang Y, Kuang Y, Paweletz C, Fu X et al (2017) Embryonic transcription factor SOX9 drives breast cancer endocrine resistance. Proc Natl Acad Sci U S A 114(22):E4482-e4491. https://doi.org/10.1073/pnas.1620993114
doi: 10.1073/pnas.1620993114
pubmed: 28507152
pmcid: 5465894
Kulkarni M, Tan TZ, Syed Sulaiman NB, Lamar JM, Bansal P, Cui J, Qiao Y, Ito Y (2018) RUNX1 and RUNX3 protect against YAP-mediated EMT, stem-ness and shorter survival outcomes in breast cancer. Oncotarget 9(18):14175–14192. https://doi.org/10.18632/oncotarget.24419
doi: 10.18632/oncotarget.24419
pubmed: 29581836
pmcid: 5865662
Lamb R, Ablett MP, Spence K, Landberg G, Sims AH, Clarke RB (2013) Wnt pathway activity in breast cancer sub-types and stem-like cells. PLoS One 8(7):e67811. https://doi.org/10.1371/journal.pone.0067811
doi: 10.1371/journal.pone.0067811
pubmed: 23861811
pmcid: 3701602
Lau QC, Raja E, Salto-Tellez M, Liu Q, Ito K, Inoue M, Putti TC, Loh M, Ko TK, Huang C et al (2006) RUNX3 is frequently inactivated by dual mechanisms of protein mislocalization and promoter hypermethylation in breast cancer. Can Res 66(13):6512–6520. https://doi.org/10.1158/0008-5472.CAN-06-0369
doi: 10.1158/0008-5472.CAN-06-0369
Li XQ, Lu JT, Tan CC, Wang QS, Feng YM (2016) RUNX2 promotes breast cancer bone metastasis by increasing integrin α5-mediated colonization. Cancer Lett 380(1):78–86. https://doi.org/10.1016/j.canlet.2016.06.007
doi: 10.1016/j.canlet.2016.06.007
pubmed: 27317874
Liang C, Zhang Z, Chen Q, Yan H, Zhang M, Zhou L, Xu J, Lu W, Wang F (2020) Centromere-localized Aurora B kinase is required for the fidelity of chromosome segregation. J Cell Biol 219(2). https://doi.org/10.1083/jcb.201907092
Liu H, Yan Z, Yin Q, Cao K, Wei Y, Rodriguez-Canales J, Ma D, Wu Y (2018) RUNX3 epigenetic inactivation is associated with estrogen receptor positive breast cancer. J Histochem Cytochem Off J Histochem Soc 66(10):709–721. https://doi.org/10.1369/0022155418797315
doi: 10.1369/0022155418797315
Liu H, Chen C, Ma D, Li Y, Yin Q, Li Q, Xiang C (2020) Inhibition of PIM1 attenuates the stem cell-like traits of breast cancer cells by promoting RUNX3 nuclear retention. J Cell Mol Med 24(11):6308–6323. https://doi.org/10.1111/jcmm.15272
Lund AH, van Lohuizen M (2002) RUNX: a trilogy of cancer genes. Cancer Cell 1(3):213–215. https://doi.org/10.1016/s1535-6108(02)00049-1
doi: 10.1016/s1535-6108(02)00049-1
pubmed: 12086855
Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS et al (2022) Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med 387(1):9–20. https://doi.org/10.1056/NEJMoa2203690
doi: 10.1056/NEJMoa2203690
pubmed: 35665782
pmcid: 10561652
Pan H, Gray R, Braybrooke J, Davies C, Taylor C, McGale P, Peto R, Pritchard KI, Bergh J, Dowsett M et al (2017) 20-Year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med 377(19):1836–1846. https://doi.org/10.1056/NEJMoa1701830
doi: 10.1056/NEJMoa1701830
pubmed: 29117498
pmcid: 5734609
Pan Y, Tong JHM, Kang W, Lung RWM, Chak WP, Chung LY, Wu F, Li H, Yu J, Chan AWH et al (2018) EXOSC4 functions as a potential oncogene in development and progression of colorectal cancer. Mol Carcinog 57(12):1780–1791. https://doi.org/10.1002/mc.22896
doi: 10.1002/mc.22896
pubmed: 30155936
Park SY, Kwon HJ, Lee HE, Ryu HS, Kim SW, Kim JH, Kim IA, Jung N, Cho NY, Kang GH (2011) Promoter CpG island hypermethylation during breast cancer progression. Virchows Arch 458(1):73–84. https://doi.org/10.1007/s00428-010-1013-6
doi: 10.1007/s00428-010-1013-6
pubmed: 21120523
Park SY, Kwon HJ, Choi Y, Lee HE, Kim SW, Kim JH, Kim IA, Jung N, Cho NY, Kang GH (2012) Distinct patterns of promoter CpG island methylation of breast cancer subtypes are associated with stem cell phenotypes. Mod Pathol 25(2):185–196. https://doi.org/10.1038/modpathol.2011.160
doi: 10.1038/modpathol.2011.160
pubmed: 22037257
Paul AM, Amjesh R, George B, Sankaran D, Sandiford OA, Rameshwar P, Pillai MR, Kumar R (2022) The revelation of continuously organized, co-overexpressed protein-coding genes with roles in cellular communications in breast cancer. Cells 11(23). https://doi.org/10.3390/cells11233806
Sakunrangsit N, Ketchart W (2019) Plumbagin inhibits cancer stem-like cells, angiogenesis and suppresses cell proliferation and invasion by targeting Wnt/β-catenin pathway in endocrine resistant breast cancer. Pharmacol Res 150:104517. https://doi.org/10.1016/j.phrs.2019.104517
doi: 10.1016/j.phrs.2019.104517
pubmed: 31693936
Schettini F, Chic N, Brasó-Maristany F, Paré L, Pascual T, Conte B, Martínez-Sáez O, Adamo B, Vidal M, Barnadas E et al (2021) Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer. NPJ Breast Cancer 7(1):1. https://doi.org/10.1038/s41523-020-00208-2
doi: 10.1038/s41523-020-00208-2
pubmed: 33397968
pmcid: 7782714
Semina SE, Alejo LH, Chopra S, Kansara NS, Kastrati I, Sartorius CA, Frasor J (2022) Identification of a novel ER-NFĸB-driven stem-like cell population associated with relapse of ER+ breast tumors. Breast Cancer Res 24(1):88. https://doi.org/10.1186/s13058-022-01585-1
doi: 10.1186/s13058-022-01585-1
pubmed: 36482488
pmcid: 9733334
Siegel RL, Giaquinto AN, Jemal A (2024) Cancer statistics, 2024. CA Cancer J Clin 74(1):12–49. https://doi.org/10.3322/caac.21820
doi: 10.3322/caac.21820
pubmed: 38230766
Skidmore L, Sakamuri S, Knudsen NA, Hewet AG, Milutinovic S, Barkho W, Biroc SL, Kirtley J, Marsden R, Storey K et al (2020) ARX788, a site-specific Anti-HER2 antibody-drug conjugate, demonstrates potent and selective activity in HER2-low and T-DM1-resistant breast and gastric cancers. Mol Cancer Ther 19(9):1833–1843. https://doi.org/10.1158/1535-7163.Mct-19-1004
doi: 10.1158/1535-7163.Mct-19-1004
pubmed: 32669315
Sun X, Xu C, Xiao G, Meng J, Wang J, Tang SC, Qin S, Du N, Li G, Ren H et al (2018) Breast cancer stem-like cells are sensitized to tamoxifen induction of self-renewal inhibition with enforced Let-7c dependent on Wnt blocking. Int J Mol Med 41(4):1967–1975. https://doi.org/10.3892/ijmm.2018.3388
doi: 10.3892/ijmm.2018.3388
pubmed: 29336465
pmcid: 5810214
Takebe N, Miele L, Harris PJ, Jeong W, Bando H, Kahn M, Yang SX, Ivy SP (2015) Targeting notch, hedgehog, and wnt pathways in cancer stem cells: clinical update. Nat Rev Clin Oncol 12(8):445–464. https://doi.org/10.1038/nrclinonc.2015.61
doi: 10.1038/nrclinonc.2015.61
pubmed: 25850553
pmcid: 4520755
Tang L, Gao Y, Song Y, Li Y, Li Y, Zhang H, Li D, Li J, Liu C, Li F (2020) PAK4 phosphorylating RUNX1 promotes ERα-positive breast cancer-induced osteolytic bone destruction. Int J Biol Sci 16(12):2235–2247. https://doi.org/10.7150/ijbs.47225
doi: 10.7150/ijbs.47225
pubmed: 32549768
pmcid: 7294946
Taniue K, Tanu T, Shimoura Y, Mitsutomi S, Han H, Kakisaka R, Ono Y, Tamamura N, Takahashi K, Wada Y et al (2022) RNA exosome component EXOSC4 amplified in multiple cancer types is required for the cancer cell survival. Int J Mol Sci 23(1). https://doi.org/10.3390/ijms23010496
Tran B, Bedard PL (2011) Luminal-B breast cancer and novel therapeutic targets. Breast Cancer Res 13(6):221. https://doi.org/10.1186/bcr2904
doi: 10.1186/bcr2904
pubmed: 22217398
pmcid: 3326541
Vas AC, Clarke DJ (2008) Aurora B kinases restrict chromosome decondensation to telophase of mitosis. Cell Cycle (Georgetown Tex) 7(3):293–296. https://doi.org/10.4161/cc.7.3.5381
doi: 10.4161/cc.7.3.5381
pubmed: 18235246
Wang YX, Li YZ, Zhu HF, Zhang ZY, Qian XL, He GY (2020) STX2 drives colorectal cancer proliferation via upregulation of EXOSC4. Life Sci 263:118597. https://doi.org/10.1016/j.lfs.2020.118597
doi: 10.1016/j.lfs.2020.118597
pubmed: 33075373
Xiong C, Sun Z, Yu J, Lin Y (2021) Exosome component 4 promotes epithelial ovarian cancer cell proliferation, migration, and invasion via the wnt pathway. Front Oncol 11:797968. https://doi.org/10.3389/fonc.2021.797968
doi: 10.3389/fonc.2021.797968
pubmed: 34956910
pmcid: 8692763
Xu X, Zhang M, Xu F, Jiang S (2020) Wnt signaling in breast cancer: biological mechanisms, challenges and opportunities. Mol Cancer 19(1):165. https://doi.org/10.1186/s12943-020-01276-5
doi: 10.1186/s12943-020-01276-5
pubmed: 33234169
pmcid: 7686704
Xue Y, Lai L, Lian W, Tu X, Zhou J, Dong P, Su D, Wang X, Cao X, Chen Y et al (2019) SOX9/FXYD3/Src Axis Is Critical for ER(+) breast cancer stem cell function. Mol Cancer Res 17(1):238–249. https://doi.org/10.1158/1541-7786.Mcr-18-0610
doi: 10.1158/1541-7786.Mcr-18-0610
pubmed: 30206184