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

Zhanguo Zhang, Yuxin Zhang, Lei Zhang, et al

Abstract


Objective: Incomplete radiofrequency ablation (ICR) has been proposed as a major cause of recurrence in the treatment of hepaticmetastatic 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 ofrecurrence of CRLMs with ICR. Here we focused on heat shock-induced CRC malignancy. Sub-lethal heat shock (HS) in CRC celllines 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 withthe untreated CRC cells. Silencing Fra-1 reversed the tumor promoting effects of HS. Furthermore, proliferation and tumorinitiation inducer c-Myc, together with tumor invasion inducer matrix-metalloprotase 1 (MMP-1) expression were up-regulatedby 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 apotential prognostic marker and a promising therapeutic strategy to prevent disease recurrence after radiofrequency ablationtreatment.

 

Cite this article as: Zhang Z, Zhang Y, Zhang L, Pei Y, Wu Y, Liang H, et al.Incomplete radiofrequency ablation provokes colorectal cancer livermetastases through heat shock response by PKCα/Fra-1 pathway. Cancer BiolMed. 2019; 16: 542-55. doi: 10.20892/j.issn.2095-3941.2018.0407


Keywords


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

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