MAP1S-mediated TLR5 signaling induces autophagic cell death to inhibit breast cancer

Abstract

Abstract TLR5 signaling in breast cancer showed strong anti-tumor activity, which might represent a novel strategy in cancer immunotherapy. However, the underlying mechanism of TLR5 signaling-based tumor suppression is still not elucidated. Here, we found TLR5 agonist flagellin could induce excessive autophagy in breast cancer cells, and the expression level of autophagic adaptor MAP1S was elevated in response to flagellin treatment. Moreover, the elevated level of MAP1S robustly promoted tumor cell death in a TLR-dependent manner. Whereas MAP1S deletion led to decreased proinflamatory cytokines expression that induced by TLR5 signaling and blockage of autophagic process in breast cancer cells. In addition, MAP1S promoted the inhibition of inflammasome pathway and pyroptosis by TLR5 signaling. Therefore, we deducted that MAP1S played a key role in TLR5 signaling-based tumor suppression. Taken together, these results indicated a mechanism of antitumor activity that involved MAP1S-mediated TLR5 signaling in breast cancer.