Striatins and STRIPAK complex partners in clinical outcomes of patients with breast cancer and responses to drug treatment

Amber Xinyu Li; Jimmy Jianyuan Zeng; Tracey A Martin; Lin Ye; Fiona Ruge; Andrew J Sanders; Elyas Khan; Q Ping Dou; Eleri Davies; Wen G Jiang

doi:10.21147/j.issn.1000-9604.2023.04.04

Striatins and STRIPAK complex partners in clinical outcomes of patients with breast cancer and responses to drug treatment

Chin J Cancer Res. 2023 Aug 30;35(4):365-385. doi: 10.21147/j.issn.1000-9604.2023.04.04.

Authors

Amber Xinyu Li¹, Jimmy Jianyuan Zeng¹, Tracey A Martin¹, Lin Ye¹, Fiona Ruge¹, Andrew J Sanders^{1

2}, Elyas Khan³, Q Ping Dou^{1

3}, Eleri Davies⁴, Wen G Jiang¹

Affiliations

¹ Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
² School of Natural and Social Science, University of Gloucestershire, Francis Close Hall, Cheltenham GL50 4AZ, UK.
³ Karmanos Cancer Institute, Department of Oncology, School of Medicine, Wayne State University, Detroit MI 48201, USA.
⁴ Wales Breast Center, Cardiff and Vales University Health Board, University Llandough Hospital, Cardiff CF64 2XX, UK.

PMID: 37691891
PMCID: PMC10485918
DOI: 10.21147/j.issn.1000-9604.2023.04.04

Abstract

Objective: Striatins (STRNs) family, which contains three multi-domain scaffolding proteins, are cornerstones of the striatins interacting phosphatase and kinase (STRIPAK) complex. Although the role of the STRIPAK complex in cancer has become recognized in recent years, its clinical significance in breast cancer has not been fully established.

Methods: Using a freshly frozen breast cancer tissue cohort containing both cancerous and adjacent normal mammary tissues, we quantitatively evaluated the transcript-level expression of all members within the STRIPAK complex along with some key interacting and regulatory proteins of STRNs. The expression profile of each molecule and the integrated pattern of the complex members were assessed against the clinical-pathological factors of the patients. The Cancer Genome Atlas (TCGA) dataset was used to evaluate the breast cancer patients' response to chemotherapies. Four human breast cancer cell lines, MDA-MB-231, MDA-MB-361, MCF-7, and SK-BR-3, were subsequently adopted for in vitro work.

Results: Here we found that high-level expressions of STRIP2, calmodulin, CCM3, MINK1 and SLMAP were respectively associated with shorter overall survival (OS) of patients. Although the similar pattern observed for STRN3, STRN4 and a contrary pattern observed for PPP2CA, PPP2CB and PPPR1A were not significant, the integrated expression profile of STRNs group and PPP2 group members constitutes a highly significant prognostic indicator for OS [P<0.001, hazard ratio (HR)=2.04, 95% confidence interval (95% CI), 1.36-3.07] and disease-free survival (DFS) (P=0.003, HR=1.40, 95% CI, 1.12-1.75). Reduced expression of STRN3 has an influence on the biological functions including adhesiveness and migration. In line with our clinical findings, the breast cancer cells responded to STRN3 knockdown with changes in their chemo-sensitivity, of which the response is also breast cancer subtype dependent.

Conclusions: Our results suggest a possible role of the STRIPAK complex in breast cancer development and prognosis. Among the members, the expression profile of STRN3 presents a valuable factor for assessing patients' responses to drug treatment.

Keywords: STRIPAK; STRN3; Striatins; breast cancer; chemo-resistance; prognosis.