Conclusions
Our study demonstrated that ICR generated HS induces CRC malignancy by targeting Fra-1, which could be a potential prognostic marker and a promising therapeutic strategy to prevent disease recurrence after radiofrequency ablation treatment.
Methods
We have established a mouse model of radiofrequency ablation (RFA) therapy to demonstrate increased risk of recurrence of CRLMs with ICR. Here we focused on heat shock-induced CRC malignancy. Sub-lethal heat shock (HS) in CRC cell lines provoked cell growth, invasion, and tumor initiation in vitro and in vivo.
Objective
Incomplete radiofrequency ablation (ICR) has been proposed as a major cause of recurrence in the treatment of hepatic metastatic tumors. We tried to determine the mechanisms of this progression in colorectal cancer (CRC) liver metastasis (CRLMs).
Results
We found that Fra-1, which lies downstream of PKCα-ERK1/2 signaling, was significantly increased by HS compared with the untreated CRC cells. Silencing Fra-1 reversed the tumor promoting effects of HS. Furthermore, proliferation and tumor initiation inducer c-Myc, together with tumor invasion inducer matrix-metalloprotase 1 (MMP-1) expression were up-regulated by AP-1/Fra-1 induced genes transcription. Conclusions: Our study demonstrated that ICR generated HS induces CRC malignancy by targeting Fra-1, which could be a potential prognostic marker and a promising therapeutic strategy to prevent disease recurrence after radiofrequency ablation treatment.