TY  - JOUR
A1  - Juratli, Mazen A.
A1  - Zhou, He
A1  - Oppermann, Elsie
A1  - Bechstein, Wolf Otto
A1  - Pascher, Andreas
A1  - Chun, Felix
A1  - Jüngel, Eva
A1  - Rutz, Jochen
A1  - Blaheta, Roman A.
T1  - Integrin alpha2 and beta1 cross-communication with mTOR/AKT and the CDK-cyclin axis in hepatocellular carcinoma cells
T2  - Cancers
N2  - Integrin receptors contribute to hepatocellular carcinoma (HCC) invasion, while AKT-mTOR signaling controls mitosis. The present study was designed to explore the links between integrins and the AKT-mTOR pathway and the CDK-Cyclin axis. HCC cell lines (HepG2, Huh7, Hep3B) were stimulated with soluble collagen or Matrigel to activate integrins, or with insulin-like growth factor 1 (IGF1) to activate AKT-mTOR. HCC growth, proliferation, adhesion, and chemotaxis were evaluated. AKT/mTOR-related proteins, proteins of the CDK-Cyclin axis, focal adhesion kinase (FAK), and integrin-linked kinase (ILK) were determined following IGF1-stimulation or integrin knockdown. Stimulation with collagen or Matrigel increased tumor cell growth and proliferation. This was associated with significant alteration of the integrins α2, αV, and β1. Blockade of these integrins led to cell cycle arrest in G2/M and diminished the number of tumor cell clones. Knocking down the integrins α2 or β1 suppressed ILK, reduced FAK-phosphorylation and diminished AKT/mTOR, as well as the proteins of the CDK-Cyclin axis. Activating the cells with IGF1 enhanced the expression of the integrins α2, αV, β1, activated FAK, and increased tumor cell adhesion and chemotaxis. Blocking the AKT pathway canceled the enhancing effect of IGF on the integrins α2 and β1. These findings reveal that HCC growth, proliferation, and invasion are controlled by a fine-tuned network between α2/β1-FAK signaling, the AKT-mTOR pathway, and the CDK–Cyclin axis. Concerted blockade of the integrin α2/β1 complex along with AKT-mTOR signaling could, therefore, provide an option to prevent progressive dissemination of HCC.
KW  - hepatocellular carcinoma
KW  - AKT-mTOR pathway
KW  - integrins
KW  - growth
KW  - invasion
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/81913
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-819133
SN  - 2072-6694
N1  - This work was supported by grants from the Rudolf Geißendörfer-Stiftung, Nachwuchsförderung/Frankfurter Forschungs Förderung (FFF), and the B. Braun-Stiftung.
VL  - 14
IS  - 10, art. 2430
SP  - 1
EP  - 17
PB  - MDPI
CY  - Basel
ER  -