自噬是肿瘤细胞产生耐药的重要途径。我们前期研究证实自噬参与前列腺癌细胞产生CRPC的过程，同时微管相关蛋白MAP1S在产生CRPC的过程中对自噬起到促进作用，从而促进前列腺癌进展，而在临床随访中证实MAP1S可以抑制前列腺癌进展。MAP1S在体内外环境中对前列腺癌的相反作用机制不明。我们前期研究证实MAP1S可抑制焦亡，而焦亡可分泌炎症因子，募集TAM，促进前列腺癌的进展。因此我们推测：在CRPC产生过程中，MAP1S通过促进细胞自噬，使前列腺癌适应去势状态产生CRPC；增强的自噬可抑制炎症体NLRP3对Caspase-1的激活，从而抑制焦亡的发生，减少TAM募集，弱化炎症反应，抑制炎-癌转化的发生。MAP1S的两种作用在体内以抑制焦亡为主。本项目拟在体内外实验中通过Elisa、Co-IP、银染质谱鉴定、免疫印记、免疫荧光及电镜等技术来探讨MAP1S对自噬、焦亡及TAM的调控机制。

Autophagy has a critical role in maintaining cell stability, and is an important way of tumor cells drug resistance. Our previous studies have confirmed the participation of autophagy during the generation of castration-resistant prostate cancer (CRPC), while microtubule associated protein (MAP1S) in the generation of the CRPC play a catalytic role for autophagy, and autophagy promote the progression of CRPC. But in the clinical follow-up confirmed MAP1S can inhibit prostate cancer disease progression. The opposite mechanism of MAP1S in vivo and in vitro is unclear. Our previous study confirmed that MAP1S can inhibit Pyroptosis,and Pyroptosis can secrete inflammatory cytokines, attract Macrophage to tumour and transform to tumour associated Macrophage(TAM), promote the progression of prostate cancer. We hypothesized that: in CRPC producing process, MAP1S promotes prostate cancer through autophagy, make prostate cancer cells adapt to castrate, resulting in CRPC. Also enhanced autophagy can inhibit inflammation NLRP3 to activate Caspase-1, thereby inhibiting the Pyroptosis, reduce the gather of TAM in cancer tissue, so as to reduce the inflammation in prostate cancer, inhibit inflammation-cancer transformation. The main effect of MAP1S in vivo is inhibiting Pyroptosis, the secondary effect is promoting CRPC by autophagy. The project plans on the basis of the preliminary study in vitro and in vivo experiment suppressed or enhanced MAP1S, LC3, autophagy, caspase-1, NLRP3 etc. by ELISA, co-IP, silver staining, mass spectrometry and electron microscopy, immunoblotting, immunofluorescence and electron microscopy technique to investigate the MAP1S regulatory mechanism of autophagy, Pyroptosis and TAM.