Insulin-like growth factor-1 influences prostate cancer cell growth and invasion through an integrin alpha3, alpha5, alphaV, and beta1 dependent mechanism
- Insulin-like growth factor-1 (IGF-1)-related signaling is associated with prostate cancer progression. Links were explored between IGF-1 and expression of integrin adhesion receptors to evaluate relevance for growth and migration. Androgen-resistant PC3 and DU145 and androgen-sensitive LNCaP and VCaP prostate cancer cells were stimulated with IGF-1 and tumor growth (all cell lines), adhesion and chemotaxis (PC3, DU145) were determined. Evaluation of Akt/mTOR-related proteins, focal adhesion kinase (FAK) and integrin α and β subtype expression followed. Akt knock-down was used to investigate its influence on integrin expression, while FAK blockade served to evaluate its influence on mTOR signaling. Integrin knock-down served to investigate its influence on tumor growth and chemotaxis. Stimulation with IGF-1 activated growth in PC3, DU145, and VCaP cells, and altered adhesion and chemotactic properties of DU145 and PC3 cells. This was associated with time-dependent alterations of the integrins α3, α5, αV, and β1, FAK phosphorylation and Akt/mTOR signaling. Integrin blockade or integrin knock-down in DU145 and PC3 cells altered tumor growth, adhesion, and chemotaxis. Akt knock-down (DU145 cells) cancelled the effect of IGF-1 on α3, α5, and αV integrins, whereas FAK blockade cancelled the effect of IGF-1 on mTOR signaling (DU145 cells). Prostate cancer growth and invasion are thus controlled by a fine-tuned network between IGF-1 driven integrin-FAK signaling and the Akt-mTOR pathway. Concerted targeting of integrin subtypes along with Akt-mTOR signaling could, therefore, open options to prevent progressive dissemination of prostate cancer.
Verfasserangaben: | Carolin SiechORCiDGND, Jochen RutzGND, Sebastian MaxeinerGND, Timothy Grein, Marlon Sonnenburg, Igor TsaurORCiDGND, Felix ChunORCiDGND, Roman A. BlahetaORCiD |
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URN: | urn:nbn:de:hebis:30:3-820771 |
DOI: | https://doi.org/10.3390/cancers14020363 |
ISSN: | 2072-6694 |
Pubmed-Id: | https://pubmed.ncbi.nlm.nih.gov/35053528 |
Titel des übergeordneten Werkes (Englisch): | Cancers |
Verlag: | MDPI |
Verlagsort: | Basel |
Dokumentart: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Datum der Veröffentlichung (online): | 12.01.2022 |
Datum der Erstveröffentlichung: | 12.01.2022 |
Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Datum der Freischaltung: | 13.02.2024 |
Freies Schlagwort / Tag: | Akt-mTOR pathway; IGF-1; growth; integrins; invasion; prostate cancer |
Jahrgang: | 14 |
Ausgabe / Heft: | 2, art. 363 |
Aufsatznummer: | 363 |
Seitenzahl: | 23 |
Erste Seite: | 1 |
Letzte Seite: | 23 |
Institute: | Medizin |
DDC-Klassifikation: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Lizenz (Deutsch): | ![]() |