Erbin是近些年新发现的一种与ErbB2相互作用的蛋白，在细胞极性形成、维持细胞粘附等方面发挥着重要作用，但其在肿瘤发生发展尤其在结直肠癌中的作用及机制尚不清楚。前期我们发现，Erbin在部分结直肠癌细胞及部分临床结直肠癌组织标本中存在着高表达；裸鼠及Erbin基因突变小鼠相关实验表明，Erbin与结直肠癌的发生密切相关；并且，Erbin可显著地影响EGFR蛋白表达、泛素化降解途径及其信号转导；基于此，我们提出Erbin调控EGFR信号可能是其驱动结直肠癌细胞生长、增殖、侵袭、转移等恶性生物学特征的重要机制。本研究将围绕Erbin对EGFR蛋白稳定性、EGFR表达调控的影响，重点研究Erbin调控EGFR信号的机制及其在结直肠癌发展进程中的作用，并在Erbin基因突变小鼠AOM诱导肠肿瘤模型、结直肠癌临床组织标本中进行验证，从而明确Erbin/EGFR信号在结直肠癌中的作用及临床意义。

Erbin , an interacting protein of ErbB2, plays an essential role in determing cell polarity and cell adhesion. However, the underlying role and mechanism of Erbin in cancer development , especially in colorectal cancer (CRC), is still poorly clear. In our preliminary work, We found that Erbin was elevated in some colorectal cancer cells and clinical tumor samples from CRC patients, which was correlated with EGFR expression，ubiquitin-mediated EGFR degradation and EGFR signal transduction. Nude mouse and Erbin mutation mouse studies further showed that Erbin was closely related with the occurrence of CRC.Based on these findings, we here hypothesize that Erbin drives the growth, proliferation, invasion and metastasis of CRC cells through its regulation to EGFR signaling pathway. We will aim to study the regulation of Erbin to EGFR stability and EGFR gene expression,and to clarify the underlying role and molecular mechanism of Erbin-regulated EGFR signaling pathway in CRC, which will be confirmed in Erbin mutation mouse models of CRC induced by AOM and clinical samples of CRC. Ultimately, We will uncover the potential role and clinical signification of Erbin/EGFR signaling axis in CRC.