SGC-X通过激活AP-1促进三阴性乳腺癌干细胞的机制研究

乳腺癌已成为我国当前社会的重大公共健康问题；尤其是三阴性乳腺癌(TNBC)预后极差，急需发掘新的高效靶向药物和治疗方案。肿瘤干细胞（CSCs）是肿瘤发生发展、侵袭转移、放化疗抵抗和复发的重要原因，研究认为CSCs是较好的癌症治疗靶标。我们发现SGC-X在三阴性乳腺癌患者中高表达且与较差预后相关；临床数据分析显示SGC-X与乳腺癌干细胞高表达基因呈正相关，敲减其表达能够抑制三阴性乳腺癌细胞的迁移侵袭以及干性成球能力。基于前期实验，本研究将验证此科学假说：SGC-X在三阴性乳腺癌中高表达，并通过与G3BP1相互作用激活Ras—AP-1信号通路，促进乳腺癌干细胞并影响了癌细胞的迁移和侵袭等过程，进而导致乳腺癌的恶化。本研究项目的实施将揭示SGC-X在乳腺癌干细胞中的功能和新调控机制，对于了解TNBC发生发展具有重要意义；更重要的是，本研究也将为这种恶性乳腺癌的分子靶向治疗提供新的治疗策略。

Breast cancer has become a major public health problem in China. In particular, the prognosis of tri-negative breast cancer (TNBC) is extremely poor, and effective targeted drugs and new treatment programs are urgently needed. Tumor stem cell (CSCs) is an important cause of tumor development, invasion and metastasis, chemotherapy resistance and recurrence. Therefore, CSCs is considered to be a better target for cancer treatment. We found that SGC-X was highly expressed in clinical tri-negative breast cancer patients and was associated with poor prognosis. Large data analysis showed that SGC-X was positively correlated with the high expression genes of breast cancer stem cells, while knockdown its expression was able to inhibit the ability of migration, invasion, and particular the stemness of breast cancer cells. Based on previous experiments, this study will further validate the hypothesis: High expression of SGC-X in TNBC could activate the Ras-AP-1 signaling pathways through its interaction with G3BP1, and promote breast CSCs and the migration and invasion of cancer cells, thus affecting the development of breast cancer. This project will reveal the new regulatory mechanism of SGC-X in breast cancer stem cells, which is of great significance for understanding the development of TNBC. More importantly, this study will also provide possible new therapeutic strategies for the molecular targeted therapy of this malignant breast cancer.