University of Oulu

Wenta, T., Schmidt, A., Zhang, Q. et al. Disassembly of α6β4-mediated hemidesmosomal adhesions promotes tumorigenesis in PTEN-negative prostate cancer by targeting plectin to focal adhesions. Oncogene 41, 3804–3820 (2022).

Disassembly of α6β4-mediated hemidesmosomal adhesions promotes tumorigenesis in PTEN-negative prostate cancer by targeting plectin to focal adhesions

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Author: Wenta, Tomasz1; Schmidt, Anette1; Zhang, Qin1;
Organizations: 1Disease Networks Research Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
2Finnadvance, Oulu, Finland
3Departments of Urology, Pathology and Radiology, and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
4Fudan University Shanghai Cancer Center; Department of Biochemistry and Molecular Biology & Key Laboratory of Metabolism and Molecular Medicine of the Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, China
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 14 MB)
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Language: English
Published: Springer Nature, 2022
Publish Date: 2022-12-20


Loss of α6β4-dependent hemidesmosomal adhesions has been observed during prostate cancer progression. However, the significance and underlying mechanisms by which aberrant hemidesmosome assembly may modulate tumorigenesis remain elusive. Using an extensive CRISPR/Cas9-mediated genetic engineering approaches in different prostate cancer cell lines combined with in vivo tumorigenesis studies in mice, bone marrow-on-chip assays and bioinformatics, as well as histological analysis of prostate cancer patient cohorts, we demonstrated that simultaneous loss of PTEN and hemidesmosomal adhesions induced several tumorigenic properties including proliferation, migration, resistance to anoikis, apoptosis, and drug treatment in vitro, and increased metastatic capacity in vivo. These effects were plectin-depended and plectin was associated with actin-rich adhesions upon hemidesmosome disruption in PTEN-negative prostate cancer cells leading to activation of EGFR/PI3K/Akt- and FAK/Src-pathways. These results suggest that analysis of PTEN and hemidesmosomal proteins may have diagnostic value helping to stratify prostate cancer patients with high risk for development of aggressive disease and highlight actin-associated plectin as a potential therapeutic target specifically in PTEN/hemidesmosome dual-negative prostate cancer.

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Series: Oncogene
ISSN: 0950-9232
ISSN-E: 0950-9232
ISSN-L: 0950-9232
Volume: 41
Issue: 30
Pages: 3804 - 3820
DOI: 10.1038/s41388-022-02389-5
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: This work was funded by University of Oulu and Academy of Finland PROFI3 program and Jane and Aatos Erkko Foundation and Biocenter Finland. Open Access funding provided by University of Oulu including Oulu University Hospital.
Copyright information: © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit