在乳腺癌中，脂代谢异常与预后不良和侵袭性增强相关。目前研究显示，甲羟戊酸（MVA）途径异常激活可能与乳腺癌发展有关，然而关于MVA途径如何影响乳腺癌发展及其上游调控分子机制尚不明确。前期我们发现，与乳腺上皮细胞相比乳腺癌细胞中∆133p53表达量异常升高，过表达∆133p53显著增强乳腺癌细胞的MVA途径并促进癌细胞增殖和转移，进一步研究显示，∆133p53可显著上调SREBP1。这些结果提示，∆133p53可能通过SREBP1介导MVA途径促进乳腺癌增殖与转移。本课题拟利用TCGA数据库分析∆133p53高表达与乳腺癌的预后和转移风险相关性；明确∆133p53上调SREBP1介导MVA途径促进乳腺癌细胞增殖和转移的分子机制；采用斑马鱼异种肿瘤移植可视化模型研究MVA抑制剂他汀类药物对乳腺癌细胞增殖和转移的影响，为乳腺癌转移预防和治疗提供理论基础和潜在药物靶点。

The mevalonate (MVA) pathway is a key metabolic pathway involved in various important cellular functions. Many studies have shown that a variety of cancerous cells have a dysregulated MVA pathway. Tumor suppressor p53 plays a central role in maintaining cellular metabolic homeostasis to suppress tumor proliferation metastasis by regulating multiple metabolic pathways. The p53 pathway is ubiquitously lost in human cancer either by p53 gene mutation or by p53 inactivation. However, despite many experimental evidences showing that p53 pathway inactivation has been reported to be associated with metabolic reprogramming to promote cancer cell proliferation and metastasis, it is difficult to understand that tumors expression fully functional wild-type p53 also occurred a dysregulated MVA pathway. Recent discovery found that p53 gene encodes for many isoforms, the p53 isoformΔ133p53 is the target gene of p53, the function of Δ133p53 may have a profound impact on our understanding of p53 tumor suppressor activity. It is very interesting that Δ133p53 expression level highly elevated in breast cancer than the normal cell. More importantly, we found that Δ133p53 may promote cancer proliferation and metastasis by regulating the MVA pathway. The aims of this project are as follow:.1..To respectively identify the functions of Δ133p53 in the MVA pathway and investigate molecular mechanisms of the functions of p53 and Δ133p53 . .2..To analysis the relevance between ∆133p53 expression and breast cancer metastasis and the stains potential function in preventing breast cancer metastasis..This project result will illuminate the function of p53 isoform ∆133p53 in the lipid metabolism. And the protein isoforms of p53 may be decoded in cancer cells for design of personalized therapy.