https://doi.org/10.4081/ejh.2021.3214
Tripartite motif-containing protein 6 facilitates growth and migration of breast cancer through degradation of STUB1
Submitted: 28 December 2020
Accepted: 2 February 2021
Published: 10 March 2021
Accepted: 2 February 2021
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Supplementary: 123
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Proteins in the tripartite motif-containing protein (TRIM) family participates in carcinogenesis. However, little attention was focused on the role of TRIM6 on development of breast cancer. Expression level of TRIM6 was found to be markedly enhanced in breast cancer cells and tissues. Functional assays demonstrated that overexpression of TRIM6 promoted breast cancer progression through increase of YAP1 (Yes-associated Protein 1), while knockdown of TRIM6 suppressed in vitro breast cancer progression and in vivo tumor growth through decrease of YAP1. Co-Immunoprecipitation (co-IP) showed that TRIM6 interacted with STUB1 (stress induced phosphoprotein 1 homology and U-box containing protein 1). TRIM6 promoted ubiquitination-mediated degradation of STUB1 to promote YAP1 signaling. Overexpression of STUB1 attenuated TRIM6-induced promotion of breast cancer growth. In conclusion, TRIM6 contributed to breast cancer progression through ubiquitination-dependent proteasomal degradation of STUB1 and provocation of YAP1 pathway, providing potential therapeutic target for breast cancer.
Tong D, Zhang J, Wang X, Li Q, Liu L, Yang J, et al. MeCP2 facilitates breast cancer growth via promoting ubiquitination-mediated P53 degradation by inhibiting RPL5/RPL11 transcription. Oncogenesis 2020;9:56.
DOI: https://doi.org/10.1038/s41389-020-0239-7
Dizon DS, Krilov L, Cohen E, Gangadhar T, Ganz PA, Hensing TA, et al. Clinical cancer advances 2016: Annual report on progress against cancer from the American Society of Clinical Oncology. J Clin Oncol 2016;34:987-1011.
DOI: https://doi.org/10.1200/JCO.2015.65.8427
Cronin PA, Wang JH, Redmond HP. Hypoxia increases the metastatic ability of breast cancer cells via upregulation of CXCR4. BMC Cancer 2010;10:225.
DOI: https://doi.org/10.1186/1471-2407-10-225
Esposito D, Koliopoulos MG, Rittinger K. Structural determinants of TRIM protein function. Biochem Soc Trans 2017;45:183-91.
DOI: https://doi.org/10.1042/BST20160325
Watanabe M, Hatakeyama S. TRIM proteins and diseases. J Biochem 2017;161:135-44.
DOI: https://doi.org/10.1093/jb/mvw087
Hatakeyama S. TRIM family proteins: Roles in autophagy, immunity, and carcinogenesis. Trends Biochem Sci 2017;42:297-311.
DOI: https://doi.org/10.1016/j.tibs.2017.01.002
Bharaj P, Atkins C, Luthra P, Giraldo MI, Dawes BE, Miorin L, et al. The host E3-ubiquitin ligase TRIM6 ubiquitinates the Ebola virus VP35 protein and promotes virus replication. J Virol 2017;91:e00833-17.
DOI: https://doi.org/10.1128/JVI.00833-17
Rajsbaum R, Versteeg Gijs A, Schmid S, Maestre Ana M, Belicha-Villanueva A, Martínez-Romero C, et al. Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin ligase TRIM6 stimulates the interferon-IKKε kinase-mediated antiviral response. Immunity 2014;40:880-95.
DOI: https://doi.org/10.1016/j.immuni.2014.04.018
Sato T, Okumura F, Ariga T, Hatakeyama S. TRIM6 interacts with Myc and maintains the pluripotency of mouse embryonic stem cells. J Cell Sci.2012;125:1544.
DOI: https://doi.org/10.1242/jcs.095273
Zheng S, Zhou C, Wang Y, Li H, Sun Y, Shen Z. TRIM6 promotes colorectal cancer cells proliferation and response to thiostrepton by TIS21/FoxM1. J Exp Clin Cancer Res 2020;39:23.
DOI: https://doi.org/10.1186/s13046-019-1504-5
Jaworska AM, Wlodarczyk NA, Mackiewicz A, Czerwinska P. The role of TRIM family proteins in the regulation of cancer stem cell self-renewal. Stem Cells 2020;38:165-73.
Kawabata H, Azuma K, Ikeda K, Sugitani I, Kinowaki K, Fujii T, et al. TRIM44 is a poor prognostic factor for breast cancer patients as a modulator of NF-κB signaling. Int J Mol Sci 2017;18:1931.
DOI: https://doi.org/10.3390/ijms18091931
Tan P, Ye Y, He L, Xie J, Jing J, Ma G, et al. TRIM59 promotes breast cancer motility by suppressing p62-selective autophagic degradation of PDCD10. PLoS Biol 2018;16:e3000051.
DOI: https://doi.org/10.1371/journal.pbio.3000051
Hayer SN, Deconinck T, Bender B, Smets K, Züchner S, Reich S, et al. STUB1/CHIP mutations cause Gordon Holmes syndrome as part of a widespread multisystemic neurodegeneration: evidence from four novel mutations. Orphanet J Rare Dis 2017;12:31.
DOI: https://doi.org/10.1186/s13023-017-0580-x
Zhang L, Li Q, Xu J, Sun G, Xu Z. Cimetidine promotes STUB1-mediated degradation of tumoral FOXP3 by activating PI3K-Akt pathway in gastric cancer. Ann Transl Med 2020;8:1304.
DOI: https://doi.org/10.21037/atm-20-6070
Liu C-M, Yu C-C, Lin T, Liao Y-W, Hsieh P-L, Yu C-H, et al. E3 ligase STUB1 attenuates stemness and tumorigenicity of oral carcinoma cells via transglutaminase 2 regulation. J Formos Med Assoc 2020;119:1532-8.
DOI: https://doi.org/10.1016/j.jfma.2020.06.004
Park S-M, Park S-H, Ryu K-J, Kim I-K, Han H, Kim H-J, et al. Downregulation of CHIP promotes ovarian cancer metastasis by inducing Snail-mediated epithelial-mesenchymal transition. Mol Oncol 2019;13:1280-95.
DOI: https://doi.org/10.1002/1878-0261.12485
Chen C, Seth AK, Aplin AE. Genetic and expression aberrations of E3 ubiquitin ligases in human breast cancer. Mol Cancer Res 2006;4:695.
DOI: https://doi.org/10.1158/1541-7786.MCR-06-0182
Luan H, Mohapatra B, Bielecki TA, Mushtaq I, Mirza S, Jennings TA, et al. Loss of the nuclear pool of ubiquitin ligase CHIP/STUB1 in Breast cancer unleashes the MZF1-cathepsin pro-oncogenic program. Cancer Res 2018;78:2524-35.
DOI: https://doi.org/10.1158/0008-5472.CAN-16-2140
Cho Y, Kang H, Kim S-J, Lee S, Jee S, Ahn S, et al. Post-translational modification of OCT4 in breast cancer tumorigenesis. Cell Death Differ 2018;25:1781-95.
DOI: https://doi.org/10.1038/s41418-018-0079-6
Sun Z, Xu R, Li X, Ren W, Ou C, Wang Q, et al. Prognostic value of Yes-associated protein 1 (YAP1) in various cancers: A meta-analysis. PloS One 2015;10:e0135119.
DOI: https://doi.org/10.1371/journal.pone.0135119
Maugeri-Saccà M, Barba M, Pizzuti L, Vici P, Di Lauro L, Dattilo R, et al. The hippo transducers TAZ and YAP in breast cancer: oncogenic activities and clinical implications. Expert Rev Mol Med 2015;17:e14.
DOI: https://doi.org/10.1017/erm.2015.12
Guo L, Chen Y, Luo J, Zheng J, Shao G. YAP1 overexpression is associated with poor prognosis of breast cancer patients and induces breast cancer cell growth by inhibiting PTEN. FEBS Open Bio 2019;9:437-45.
DOI: https://doi.org/10.1002/2211-5463.12597
Sun J-G, Chen X-W, Zhang L-P, Wang J, Diehn M. Yap1 promotes the survival and self-renewal of breast tumor initiating cells via inhibiting Smad3 signaling. Oncotarget 2016;7:9692-706.
DOI: https://doi.org/10.18632/oncotarget.6655
Yu S, Zhang M, Huang L, Ma Z, Gong X, Liu W, et al. ERK1 indicates good prognosis and inhibits breast cancer progression by suppressing YAP1 signaling. Aging (Albany NY) 2019;11:12295-314.
DOI: https://doi.org/10.18632/aging.102572
Guimei M, Alrouh S, Saber-Ayad M, Hafezi SA, Vinod A, Rawat S, et al. Inhibition of Yes-associated protein-1 (YAP1) enhances the response of invasive breast cancer cells to the standard therapy. Breast Cancer (Dove Med Press) 2020;12:189-99.
DOI: https://doi.org/10.2147/BCTT.S268926
Tang D-E, Dai Y, Lin L-W, Xu Y, Liu D-Z, Hong X-P, et al. STUB1 suppresseses tumorigenesis and chemoresistance through antagonizing YAP1 signaling. Cancer Sci 2019;110:3145-56.
DOI: https://doi.org/10.1111/cas.14166
Wang Y, Ren F, Wang Y, Feng Y, Wang D, Jia B, et al. CHIP/Stub1 functions as a tumor suppressor and represses NF-κB-mediated signaling in colorectal cancer. Carcinogenesis 2014;35:983-91.
DOI: https://doi.org/10.1093/carcin/bgt393
Jang KW, Lee KH, Kim SH, Jin T, Choi EY, Jeon HJ, et al. Ubiquitin ligase CHIP induces TRAF2 proteasomal degradation and NF-κB inactivation to regulate breast cancer cell invasion. J Cell Biochem 2011;112:3612-20.
DOI: https://doi.org/10.1002/jcb.23292
Ethics Approval
All procedures performed in this study involving human participants were in accordance with the standards upheld by the Ethics Committee of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University and with those of the 1964 Helsinki Declaration and its later amendments for ethical research involving human subjects. All animal experiments were approved by the Ethics Committee of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University for the use of animals and conducted in accordance with the National Institutes of Health Laboratory Animal Care and Use GuidelinesSupporting Agencies
This work was supported by the National Natural Science Foundation of China (NSFC)How to Cite
Wei, C. ., Wu, J. ., Liu, W., Lu, J. ., Li, H. ., & Hai, B. (2021). Tripartite motif-containing protein 6 facilitates growth and migration of breast cancer through degradation of STUB1. European Journal of Histochemistry, 65(1). https://doi.org/10.4081/ejh.2021.3214
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