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). https://doi.org/10.1038/s41388-022-02389-5
Disassembly of α6β4-mediated hemidesmosomal adhesions promotes tumorigenesis in PTEN-negative prostate cancer by targeting plectin to focal adhesions
|Author:||Wenta, Tomasz1; Schmidt, Anette1; Zhang, Qin1;|
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
|Online Access:||PDF Full Text (PDF, 14 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2022122072880
|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.
|Pages:||3804 - 3820|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
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.
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