CTPS1 promotes malignant progression of triple-negative breast cancer with transcriptional activation by YBX1

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Abstract

Background

Cytidine nucleotide triphosphate synthase 1 (CTPS1) is a CTP synthase which play critical roles in DNA synthesis. However, its biological regulation and mechanism in triple-negative breast cancer (TNBC) has not been reported yet.

Methods

The expression of CTPS1 in TNBC tissues was determined by GEO, TCGA databases and immunohistochemistry (IHC). The effect of CTPS1 on TNBC cell proliferation, migration, invasion, apoptosis and tumorigenesis were explored in vivo and in vitro. In addition, the transcription factor Y-box binding protein 1 (YBX1) was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. Pearson correlation analysis was utilized to assess the association between YBX1 and CTPS1 expression.

Results

CTPS1 expression was significantly upregulated in TNBC tissues and cell lines. Higher CTPS1 expression was correlated with a poorer disease-free survival (DFS) and overall survival (OS) in TNBC patients. Silencing of CTPS1 dramatically inhibited the proliferation, migration, invasion ability and induced apoptosis of MDA-MB-231 and HCC1937 cells. Xenograft tumor model also indicated that CTPS1 knockdown remarkably reduced tumor growth in mice. Mechanically, YBX1 could bind to the promoter of CTPS1 to promote its transcription. Furthermore, the expression of YBX1 was positively correlated with CTPS1 in TNBC tissues. Rescue experiments confirmed that the enhanced cell proliferation and invasion ability induced by YBX1 overexpression could be reversed by CTPS1 knockdown.

Conclusion

Our data demonstrate that YBX1/CTPS1 axis plays an important role in the progression of TNBC. CTPS1 might be a promising prognosis biomarker and potential therapeutic target for patients with triple-negative breast cancer.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12967-021-03206-5.

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Most cited references 36

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Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)

This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.

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Triple-negative breast cancer.

William Foulkes, Ian Smith, Jorge S. Reis-Filho (2010)

Triple-negative breast cancer, so called because it lacks expression of the estrogen receptor, progesterone receptor, and HER2, is often, but not always, a basal-like breast cancer. This review focuses on its origin, molecular and clinical characteristics, and treatment.

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Is Open Access

JASPAR 2020: update of the open-access database of transcription factor binding profiles

Oriol Fornes, Jaime Castro-Mondragon, Aziz Khan … (2019)

Abstract JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) for TFs across multiple species in six taxonomic groups. In this 8th release of JASPAR, the CORE collection has been expanded with 245 new PFMs (169 for vertebrates, 42 for plants, 17 for nematodes, 10 for insects, and 7 for fungi), and 156 PFMs were updated (125 for vertebrates, 28 for plants and 3 for insects). These new profiles represent an 18% expansion compared to the previous release. JASPAR 2020 comes with a novel collection of unvalidated TF-binding profiles for which our curators did not find orthogonal supporting evidence in the literature. This collection has a dedicated web form to engage the community in the curation of unvalidated TF-binding profiles. Moreover, we created a Q&A forum to ease the communication between the user community and JASPAR curators. Finally, we updated the genomic tracks, inference tool, and TF-binding profile similarity clusters. All the data is available through the JASPAR website, its associated RESTful API, and through the JASPAR2020 R/Bioconductor package.

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Author and article information

Contributors

Chuan Wang: chuanwang1968@outlook.com

Chuangui Song: songcg1971@hotmail.com

Fangmeng Fu:

ORCID: http://orcid.org/0000-0002-3065-5708

ffm@fjmu.edu.cn

Journal

Journal ID (nlm-ta): J Transl Med

Journal ID (iso-abbrev): J Transl Med

Title: Journal of Translational Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 1479-5876

Publication date (Electronic): 6 January 2022

Publication date PMC-release: 6 January 2022

Publication date Collection: 2022

Volume: 20

Electronic Location Identifier: 17

Affiliations

[1 ]GRID grid.411176.4, ISNI 0000 0004 1758 0478, Department of Breast Surgery, , Fujian Medical University Union Hospital, ; No.29, Xin Quan Road, Gulou District, Fuzhou, 350001 Fujian China

[2 ]GRID grid.411176.4, ISNI 0000 0004 1758 0478, Department of General Surgery, , Fujian Medical University Union Hospital, ; Fuzhou, 350001 Fujian China

[3 ]GRID grid.256112.3, ISNI 0000 0004 1797 9307, Breast Cancer Institute, Fujian Medical University, ; Fuzhou, Fujian China

[4 ]GRID grid.411176.4, ISNI 0000 0004 1758 0478, Department of Pathology, , Fujian Medical University Union Hospital, ; Fuzhou, 350001 Fujian China

Author information

Fangmeng Fu http://orcid.org/0000-0002-3065-5708

Article

Publisher ID: 3206

DOI: 10.1186/s12967-021-03206-5

PMC ID: 8734240

PubMed ID: 34991621

SO-VID: 44973ae8-8df0-419b-afc4-e26312f1a21f

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 26 August 2021

Date accepted : 17 December 2021

Funding

Funded by: Joint funds for the Innovation of Science and Technology, Fujian Province

Award ID: 2018Y9205

Award ID: 2019Y9054

Award ID: 2019Y9103

Award Recipient : Jie Zhang Chuan Wang Fangmeng Fu

Funded by: FundRef http://dx.doi.org/10.13039/501100003392, Natural Science Foundation of Fujian Province;

Award ID: 2020J01995

Award Recipient : Lili Chen

Funded by: Fujian Young Teacher Education Research Project

Award ID: JAT170228

Award Recipient : Jie Zhang

Funded by: Fujian Provincial Health Technology Project

Award ID: 2020QNA039

Award Recipient : Minyan Chen

Custom metadata

ScienceOpen disciplines: Medicine

Keywords: triple-negative breast cancer,ctps1,progression,ybx1,transcriptional activation

Data availability:

ScienceOpen disciplines: Medicine

Keywords: triple-negative breast cancer, ctps1, progression, ybx1, transcriptional activation

CTPS1 promotes malignant progression of triple-negative breast cancer with transcriptional activation by YBX1

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Most cited references 36

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Triple-negative breast cancer.

JASPAR 2020: update of the open-access database of transcription factor binding profiles

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