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Perturbation of mammary epithelial cell apicobasal polarity by RHBDF1-facilitated nuclear translocation of PKCζ.

Authors :
Zhao HY
Zhu YP
Wen Y
Sun J
Ding XY
Cao XY
Wu KL
Fu L
Li LY
Source :
Biological research [Biol Res] 2024 Nov 24; Vol. 57 (1), pp. 90. Date of Electronic Publication: 2024 Nov 24.
Publication Year :
2024

Abstract

Background: The establishment of apicobasal polarity in epithelial cells is of critical importance in morphogenesis of mammary gland and other secretive gland tissues. The demise of the polarity is a critical step in early stages of tumorigenesis such as in breast ductal carcinoma in situ. The underlying molecular mechanism thus warrants in-depth investigations.<br />Results: Protein kinase C isoform ζ (PKCζ), which is highly expressed in breast cancer cells, accumulates in the nuclei of human mammary epithelial cells overexpressing human rhomboid family-1 (RHBDF1), an endoplasmic reticulum membrane protein. Nuclear translocation of PKCζ results in the failure of the formation of the cytosolic apicobasal polarity complex Par, of which PKCζ is an essential component. Additionally, enhanced nuclear translocation of PKCζ is accompanied by an inhibition of the expression of cell tight junction and adherens junction proteins and an increase of cell mobility. Mechanistically, RHBDF1 is able to interact with importin β1 and PKCζ and promote PKCζ phosphorylation. Consistently, treatment of RHBDF1-overexpressing cells with an inhibitor of PKCζ phosphorylation leads to restoration of apicobasal polarity and cell-cell junctions, as well as suppressed cell mobility.<br />Conclusions: RHBDF1-facilitated nuclear translocation of PKCζ is critically responsible for the dismantlement of epithelial cell apicobasal polarity, and thus may serve as a target in the development of therapeutic approaches against early stages of breast cancer.<br />Competing Interests: Declarations. Ethics approval and consent to participate: Breast tissue samples were collected from the full information database of breast cancer patients in the Breast Cancer Pathology and Research Laboratory of Cancer Hospital of Tianjin Medical University (Tianjin, China), including para-cancerous tissue and breast cancer tissue diagnosed as invasive breast cancer by two senior pathologists of six patients. The research procedure of this work is in line with the ethical standards of Tianjin Medical Oncology Institute and Hospital Ethics Committee. This study was approved by the Evaluation Committee of Cancer Hospital of Tianjin Medical University and all breast cancer patients were fully informed and signed the informed consent form. Conflict of interest: The authors declare no conflict of interest. Consent to participate and consent to publish: All authors consent to the publication of the data.<br /> (© 2024. The Author(s).)

Details

Language :
English
ISSN :
0717-6287
Volume :
57
Issue :
1
Database :
MEDLINE
Journal :
Biological research
Publication Type :
Academic Journal
Accession number :
39582014
Full Text :
https://doi.org/10.1186/s40659-024-00566-2