Molecular and Clinical Significance of Stanniocalcin-1 Expression in Breast Cancer Through Promotion of Homologous Recombination-Mediated DNA Damage Repair.

Jing Hou,Na Wei,Zehua Dai,Shu Wang,Huan Chen,Jigan Cheng,Qing Ni,Leilei Li,Min Dai,Hua Wang

doi:10.3389/fcell.2021.731086

Abstract

Stanniocalcin-1 (STC1) is a glycoprotein hormone whose abnormal expression has been reported to be associated with a variety of tumors, but its function in breast cancer is not well understood. Through modulation of STC1 expression in different breast cancer cell lines, our study found that STC1 could promote the proliferation and growth of breast cancer cells and promote metastasis. Furthermore, STC1 reduced apoptosis induction by irradiation. We also found that STC1 could promote a homologous recombination-mediated DNA damage repair by recruiting BRCA1 to sites of damage. Moreover, STC1 silencing sensitized breast cancer cells to treatment with irradiation (IR), olaparib, or cisplatin in vitro. In clinical settings, the serum concentration of STC1 was higher in breast cancer patients than in healthy women, as detected by enzyme-linked immunosorbent assay (ELISA). In addition, immunohistochemical staining of breast cancer specimens showed that a high expression of STC1 was negatively correlated with recurrence-free survival in breast cancer, indicating that STC1 expression could be used as a predictive marker for a poor prognosis in breast cancer. All these findings indicate that STC1 promotes breast cancer tumorigenesis and that breast cancers with a high level of STC1 are more resistant to treatment, probably through homologous recombination (HR) promotion. Furthermore, combining STC1 inhibition and DNA damage-inducing drugs may be a novel approach to improve the survival of patients with STC1-expressing breast cancer.

Highlights

Stanniocalcin (STC) is a member of the secretory glycoprotein family
It was observed that silencing STC1 expression reduced tumor growth in both murine and human breast cancer cells in vivo, but no obvious effects on proliferation were observed in either model in vitro (Chang et al, 2015), implying that the cell microenvironment is important for STC1 function
We hypothesized that STC1 may function though DNA damage repair in a BRCA1-dependent manner based on the following facts: a. the expression of STC1 in breast cancer is reported (Welcsh et al, 2002) to be related to BRCA1; b

Summary

INTRODUCTION

Stanniocalcin (STC) is a member of the secretory glycoprotein family. It was first found in fish and, in recent years, has been widely found in humans and mammals. Many studies on the relationship between STC1 and tumor development have reported contradictory conclusions. The function of STC1 in breast cancer is still elusive. Han et al (2016) found that STC1 is a prognostic indicator of triple-negative breast cancer (TNBC). Since TNBC has been reported to harbor a high probability of BRCA1 deficiency and a homologous recombination defect (HRD), we hypothesized that STC1 has an important role in DNA repair and can be used as a biomarker for DNA damage-inducing agents in breast cancer

MATERIALS AND METHODS

RESULTS

DISCUSSION

ETHICS STATEMENT