Heat treatment-induced autophagy promotes breast cancer cell invasion and metastasis via TGF-?2-mediated epithelial-mesenchymal transitions

Background. Insufficient thermal ablation can accelerate malignant behaviors and metastases in some solid tumors, and epithelial-mesenchymal transition (EMT) and autophagy are involved in tumor metastasis. It has been found that TGF-02 which belongs to the family of transforming growth factors often associated with cancer cell invasiveness and EMT. However, whether the interactions between autophagy and TGF-02 induce EMT in breast cancer (BC) cells following insufficient microwave ablation (MWA) remains unclear. Methods. BC cells were treated with sublethal heat treatment to simulate insufficient MWA, and the effects of heat treatment on the BC cell phenotypes were explored. CCK-8, colony formation, flow cytometry, Transwell, and wound healing assays were performed to evaluate the influence of sublethal heat treatment on the proliferation, apoptosis, invasion, and migration of BC cells. Western blotting, real-time quantitative PCR, immunofluorescence, and transmission electron microscopy were carried out to determine the changes in markers associated with autophagy and EMT following sublethal heat treatment. Results. Results showed that heat treatment promoted the proliferation of surviving BC cells, which was accompanied by autophagy induction. Heat treatment-induced autophagy up-regulated TGF-02/Smad2 signaling and promoted EMT phenotype, thereby enhancing BC cells' migration and invasion abilities. An increase or decrease of TGF-02 expression resulted in the potentiation and suppression of autophagy, as well as the enhancement and abatement of EMT. Autophagy inhibitors facilitated apoptosis and repressed proliferation of BC cells in vitro, and thwarted BC cell tumor growth and pulmonary metastasis in vivo. Conclusion. Heat treatment-induced autophagy promoted invasion and metastasis via TGF-02/Smad2-mediated EMTs. Suppressing autophagy may be a suitable strategy for overcoming the progression and metastasis of residual BC cells following insufficient MWA.

Automated summary

Insufficient microwave ablation (MWA) can induce autophagy and epithelial-mesenchymal transition (EMT) in breast cancer cells, leading to tumor metastasis. Heat treatment promotes the growth and metastasis of breast cancer cells through the TGF-02/Smad2-mediated EMT pathway. Inhibition of autophagy may be a suitable strategy to overcome the progression and metastasis of residual breast cancer cells following insufficient MWA.