CTSL, a prognostic marker of breast cancer, that promotes proliferation, migration, and invasion in cells in triple-negative breast cancer

Lianmei Zhang; Yang Zhao; Jing Yang; Yaning Zhu; Ting Li; Xiaoyan Liu; Pengfei Zhang; Jingliang Cheng; Suan Sun; Chunli Wei; Junjiang Fu

doi:10.3389/fonc.2023.1158087

CTSL, a prognostic marker of breast cancer, that promotes proliferation, migration, and invasion in cells in triple-negative breast cancer

Front Oncol. 2023 Jun 29:13:1158087. doi: 10.3389/fonc.2023.1158087. eCollection 2023.

Authors

Lianmei Zhang^{1

2

3}, Yang Zhao¹, Jing Yang^{2

4}, Yaning Zhu¹, Ting Li², Xiaoyan Liu², Pengfei Zhang⁵, Jingliang Cheng², Suan Sun¹, Chunli Wei², Junjiang Fu²

Affiliations

¹ Department of Pathology, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China.
² Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan, China.
³ Department of Pathology, Taizhou People's Hospital of Nanjing University of Chinese Medicine, Jiangsu, China.
⁴ Department of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, Hunan, China.
⁵ NHC Key Laboratory of Cancer Proteomics, Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Abstract

Introduction: In the world, the incidence of breast cancer has surpassed that of lung cancer, and it has become the first malignant tumor among women. Triple-negative breast cancer (TNBC) shows an extremely heterogeneous malignancy toward high recurrence, metastasis, and mortality, but there is a lack of effective targeted therapy. It is urgent to develop novel molecular targets in the occurrence and therapeutics for TNBC, and novel therapeutic strategies to block the recurrence and metastasis of TNBC.

Methods: In this study, CTSL (cathepsin L) expression in tissues and adjacent tissues of TNBC patients was monitored by immunohistochemistry and western blots. The correlations between CTSL expressions and clinicopathological characteristics in the patient tissues for TNBC were analyzed. Cell proliferation, migration, and invasion assay were also performed when over-expressed or knocked-down CTSL.

Results: We found that the level of CTSL in TNBC is significantly higher than that in the matched adjacent tissues, and associated with differentiated degree, TNM Stage, tumor size, and lymph node metastatic status in TNBC patients. The high level of CTSL was correlated with a short RFS (p<0.001), OS (p<0.001), DMFS (p<0.001), PPS (p= 0.0025) in breast cancer from online databases; while in breast cancer with lymph node-positive, high level of CTSL was correlated with a short DMFS (p<0.001) and RFS (p<0.001). Moreover, in vitro experiments showed that CTSL overexpression promotes the abilities for proliferation, migration, and invasion in MCF-7 and MDA-MB-231 cell lines, while knocking-down CTSL decreases its characteristics in MDA-MB-231 cell lines.

Conclusion: CTSL might involve into the regulation of the proliferation, invasion, and metastasis of TNBC. Thus, CTSL would be a novel, potential therapeutic, and prognostic target of TNBC.

Keywords: cell proliferation; invasion; migration; prognostics; the CTSL gene; triple-negative breast cancer (TNBC).

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant nos. 81672887 and 82073263), the Joint Innovation Special Project of Science and Technology Plan of Sichuan Province (grant nos. 2022YFS0623-C4 and 2022YFS0623-C3), the Project Fund for Young Innovative Talents of Huai’an No. 1 Hospital Affiliated to Nanjing Medical University (grant nos. QC202209), and the Primary Research & Development Plan of Hunan Province (2020SK2071).