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

IntroductionIn 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. MethodsIn 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. ResultsWe 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. ConclusionCTSL 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.

Automated summary

In this study, the expression of CTSL in TNBC tissues and adjacent tissues was monitored and analyzed for its correlation with clinicopathological characteristics. The results showed that CTSL levels were higher in TNBC and correlated with differentiation, TNM stage, tumor size, and lymph node metastasis. Moreover, in vitro experiments demonstrated that CTSL overexpression enhanced proliferation, migration, and invasion abilities in MCF-7 and MDA-MB-231 cell lines. Conversely, knockdown of CTSL decreased these characteristics in MDA-MB-231 cell line. The findings suggest that CTSL could serve as a potential therapeutic and prognostic target for TNBC.