Sugase T, et al. - Authors probed the antitumor impacts of SOCS1 gene therapy, which targeted several signaling pathways in imatinib-resistant gastrointestinal stromal tumors (GIST) cells through focal adhesion kinase (FAK)/PI3 K signaling. For proliferation of both imatinib-sensitive and -resistant GIST cells, the activation of FAK signaling was seen to be critical. For therapeutic target, the interference with FAK/AKT pathway could be beneficial.

Methods

• Experts used GIST-T1 (imatinib-sensitive) and GIST-R8 (imatinib-resistant) cells.
• Both cell lines were infected with an adenovirus expressing SOCS1 (AdSOCS1) and they examined antitumor effect and mechanisms of its agent.

Results

• Findings suggested that the latter harboured with secondary KIT mutation and demonstrated the imatinib resistance > 1000-fold higher than the former cells.
• AdSOCS1 was seen to significantly decrease the proliferation and induce apoptosis in both cell lines.
• Furthermore, the phosphorylation of signal transducer and activator of transcription 3 (STAT3), AKT, and focal adhesion kinase (FAK) was inhibited by SOCS1 overexpression in both of them.
• As per the data, the proliferation was not affected enough by inhibition of JAK signaling.
• Nonetheless, inhibitory effect on cell growth and suppression of the phosphorylation of AKT was significantly demonstrated with the inhibition of the FAK signaling with an FAK inhibitor or RNA interference, indicating a cross-talk between the AKT and FAK pathways in both the imatinib-sensitive and imatinib-resistant GIST cells.