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

Xinyu Li, Amber, Jianyuan Zeng, Jimmy, Martin, Tracey A, Ye, Lin, Ruge, Fiona, Sanders, Andrew J ORCID: 0000-0002-7997-5286, Khan, Elyas, Ping Dou, Q, Davies, Eleri and Jiang, Wen G (2023) Striatins and STRIPAK complex partners in clinical outcomes of patients with breast cancer and responses to drug treatment. Chinese Journal of Cancer Research, 35 (4). pp. 365-385. doi:10.21147/j.issn.1000-9604.2023.04.04

Text 13174 Xinyu Li, Jianyuan Zeng, Martin, Ye, Ruge, Sanders, Khan, Ping Dou, Davies, Jiang (2023) Striatins and STRIPAK complex partners in clinical outcomes of patients with breast cancer and responses to drug treatment.pdf - Accepted Version Restricted to Repository staff only Available under License All Rights Reserved. Download (1MB)

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.

Item Type:	Article
Article Type:	Article
Additional Information:	The full text of the published article has been made freely available via the journal's website; follow DOI link to view.
Uncontrolled Keywords:	Striatins; STRN3; STRIPAK; Breast cancer; Prognosis; Chemo-resistance
Subjects:	Q Science > QR Microbiology R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions:	Schools and Research Institutes > School of Education and Science
Research Priority Areas:	Place, Environment and Community
Depositing User:	Anna Kerr
Date Deposited:	11 Oct 2023 10:39
Last Modified:	12 Oct 2023 09:15
URI:	https://eprints.glos.ac.uk/id/eprint/13174

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