Flightless I as a molecular target to inhibit radiation-induced colorectal cancer metastasis.

Abstract

Exposure to radiation is expected to inhibit the proliferation of cancer cells, but sometimes cells are resistant to ionizing radiation. This condition can lead to cancer cell metastasis and recurrence. The mechanisms leading to the development of radioresistance are not yet fully understood. Therefore, this study aims to determine the involvement of a cytoskeletal protein, Flightless I (FliI), in cancer progression and to assess the effect of radiation exposure on the role and functionality of FliI in HCT116 cells. The expression of FliI was measured in HCT116 cells, transfected with siRNA to reduce FliI activity, and validated by Western Blot. The colony formation assay revealed a significant difference in the number of cells forming colonies on FliI-silenced cells following exposure to 6 Gy radiation. Transwell migration and invasion assays shows that silencing FliI in HCT116 cells make the m less able to migrate and invade. Further investigation via a gelatin degradation assay revealed a significant reduction in the number of cells forming invadopodia in FliI-silenced HCT116 cells compared to controls. We proved the efficacy of FliI in inhibiting radiation-enhanced cancer migration and invasion, indicating its potential as a therapeutic target to enhance radiosensitization in CRC patients.