EGFR非酪氨酸激酶途径的信号分子SGLT1下调可致细胞自噬性死亡，为研究Cetuximab抗瘤机制的新方向！我们已发现Cetuximab下调结肠癌细胞SGLT1而诱导自噬；肠癌组织中自噬标志物LC3表达与Cetuximab疗效相关；相关内容发表论文10余篇(5篇SCI)。自噬的主要信号通路是mTOR与Beclin1，预实验证实Beclin1不参与Cetuximab诱导自噬。本课题研究Cetuximab是否通过SGLT1/AMPK介导的mTOR路径诱发肠癌细胞自噬；SGLT1是否为激活AMPK的新途径；干预AMPK、mTOR及p70S6k是否增敏Cetuximab抑制细胞增殖和这些分子在癌组织的表达对Cetuximab疗效的预测价值；旨在从自噬角度阐明Cetuximab新的抗瘤机制，探索Cetuximab疗效新的预测指标，为下一步干预自噬增敏Cetuximab联合化疗疗效研究提供实验基础。

Autophagy could serve as a newt anti-cancer mechanism of Cetuximab since downregulating decsodium/glucose cotransporter 1 (SGLT1) in kinase-independent EGFR pathway could trigger autophagic cell death. We have found that cetuximab induced autophagy by down regulating the expression of SGLT1 and that the expression of LC3, a marker of autophagy, showed a correlation with the efficacy of cetuximab, so more than ten papers were published in professional publications, including 5 SCI papers. The mTOR complex as well as Beclin1 complex is the major factor serving as regulation signals and transduction pathways in the process of autophagy, while our pilot experiments showed that Beclin1 had no role in the autophagy induced by Cetuximab. We plan to explore whether that autophagy by Cetuximab is dependent on the pathway of mTOR through Cetuximab regulating SGLT1 and AMPK, and to clarify if SGLT1 is another new way to active AMPK, and show if interposing AMPK, mTOR and p70S6k could sensitize Cetuximab, while analysis the correlations between their expression in colorectal cancer with the effect of cetuximab, therefore find the newest anti-cancer mechanism of Cetuximab by studying autophagy, and explore the new molecular indicator for the efficacy of Cetuximab, and provide theoretical basis for the next research program of improving the effect of cetuximab combined with the chemotherapy through interposing the autophagy.