Elevated expression of CST1 promotes breast cancer progression and predicts a poor prognosis

Abstract

Cystatin SN (CST1) belongs to the type 2 cystatin (CST) superfamily, which restricts the proteolytic activities of cysteine proteases. CST1 has been recently considered to be involved in the development of several human cancers. However, the prognostic significance and function of CST1 in breast cancer remains unknown. In the current study, we found that CST1 was generally upregulated in breast cancer at both mRNA and protein level. Furthermore, overall survival (OS) and disease-free survival (DFS) in the low CST1 expression subgroup were significantly superior to the high CST1 expression subgroup (OS, p < 0.001; DFS, p < 0.001), which indicated that CST1 expression level was closely correlated to the survival risk of these patients. Univariate and multivariate analyses demonstrated that CST1 expression was an independent prognostic factor, the same as ER status and nodal status. Next, CST1 overexpression promoted breast cancer cell proliferation, clonogenicity, migration, and invasion abilities. By contrast, knockdown of CST1 attenuated these malignant characteristics in breast cancer cells. Collectively, our study indicates that CST1 cannot only serve as a significant prognostic indicator but also as a potential therapeutic target for breast cancer.Key messages High CST1 expression is negatively correlated with survival of breast cancer patients.CST1 promotes cell proliferation, clone formation, and metastasis in breast cancer cells.CST1 is a novel potential prognostic biomarker and therapeutic target for breast cancer. Electronic supplementary materialThe online version of this article (doi:10.1007/s00109-017-1537-1) contains supplementary material, which is available to authorized users.

Functional role of RRS1 in breast cancer cell proliferation

“…The staining intensity of RRS1 expression was scored according to the following: score 0, negative staining; score 1, weak staining; score 2, moderate staining; and score 3, strong staining; the extent of staining was classified as the percentage of positive cells: score 0, 0; score 1, 1‐25%; score 2, 26‐50%; score 3, 51‐75%; and score 4, 76‐100%. The final quantitation of staining for each sample was obtained by multiplying the two scores . RRS1 expression was graded as high expression if the score >6; if the score ≤6, the case was classified as low expression.…”

Peer Review #1 of "Evidence for an oncogenic role of HOXC6 in human non-small cell lung cancer (v0.2)"

“…Consistent with this result, we found that HOXC6 is a master regulator of many genes, which have documented pro-tumorigenic functions. In our studies, we identified several genes, including CEACAM6, SPARC, WNT6, CST1, MMP2, and KRT13, which have been extensively studied and demonstrated to be involved in the regulation of tumor growth, migration and invasion, cell cycle, and apoptosis (Chang et al 2018;Choi et al 2009;Dai et al 2017;Kuo et al 2014;Rizeq et al 2018;Wang et al 2018;Yusuf et al 2014;. In other types of cancers, HOXC6 has also been shown to have the capacity to regulate these cancerrelated genes.…”

LINC01857 as an oncogene regulates CREB1 activation by interacting with CREBBP in breast cancer

“…Breast cancer had serious adverse effects on the prognosis of patients (Dai et al, 2017). In recent years, proposal of molecular biomarkers had provided important clues for targeted therapy of breast cancer as well as other malignant tumors (Buzdin et al, 2018;Kutomi et al, 2017).…”