Incomplete radiofrequency ablation provokes colorectal cancer liver metastases through heat shock response by PKCα/Fra-1 pathway

【Author】

Zhanguo Zhang;Yuxin Zhang;Lei Zhang;Youliang Pei;Yanhui Wu;Huifang Liang;Wanguang Zhang;Bixiang Zhang;Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Clinical Medicine Research Center for Hepatic Surgery;

【Institution】

Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Clinical Medicine Research Center for Hepatic Surgery;

【Abstract】

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)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.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.

【Keywords】

Radiofrequency ablation;;heat shock;;colorectal cancer liver metastases;;cancer stem cells;;recurrence

References

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Springer Journals Database

Total: 21 articles

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