TY  - JOUR
A1  - Siech, Carolin
A1  - Rutz, Jochen
A1  - Maxeiner, Sebastian
A1  - Grein, Timothy
A1  - Sonnenburg, Marlon
A1  - Tsaur, Igor
A1  - Chun, Felix
A1  - Blaheta, Roman A.
T1  - Insulin-like growth factor-1 influences prostate cancer cell growth and invasion through an integrin alpha3, alpha5, alphaV, and beta1 dependent mechanism
T2  - Cancers
N2  - 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.
KW  - prostate cancer
KW  - IGF-1
KW  - Akt-mTOR pathway
KW  - integrins
KW  - growth
KW  - invasion
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/82077
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-820771
SN  - 2072-6694
VL  - 14
IS  - 2, art. 363
SP  - 1
EP  - 23
PB  - MDPI
CY  - Basel
ER  -