肿瘤组织中EGFR往往呈现高表达或信号过度活化，且EGFR过表达比突变更为常见。多数情况下，EGFR表达量与其基因拷贝数并不直接相关，表明EGFR的过表达可能是由于降解异常所致。过表达的EGFR促进肿瘤恶性进展和耐药发生，因此，直接调节 EGFR 蛋白稳定性成为开发靶向 EGFR 抗肿瘤药物的新策略。TRB3是一种应激诱导蛋白，在多种肿瘤中高表达。我们最近发现，敲低肝癌细胞中TRB3表达能抑制肿瘤生长和转移，并显著降低EGFR表达量。TRB3能与EGFR相互作用，抑制EGFR降解。但TRB3调节EGFR的机制尚不明确。为此，我们将采用体内和体外模型，从分子-细胞-动物三个层次，确定TRB3是否通过调节EGFR发挥促肿瘤效应及参与肿瘤耐药，并阐明TRB3调节EGFR稳定性的分子机制。本研究不但有助于揭示EGFR稳定性调节的机制，也将为抗肿瘤药物研发提供新的思路。

Studies on a series of tumors revealed that EGFR overexpression was the most frequent EGFR-related abnormality, whereas EGFR mutation was a minor event. In most cases, the expression level of EGFR is not directly related with its gene copies, suggesting that EGFR overexpression may be caused by degradation abnormality.Aberrant expression of EGFR not only promotes tumor progression, but also participates in therapy resistance. So targeting EGFR stability is becoming a new strategy for developing anti-cancer drugs.TRB3 is an intracellular stress sensor with high expression in several tumor cells. Recently, we found that depletion of TRB3 in hepatocellular carcinoma cells can inhibit tumor proliferation and metastasis. Furthermore, EGFR expression was reduced significantly when depletion of TRB3. TRB3 can interact with EGFR and inhibit its degradation. However the mechanisms of TRB3 in the regulation of EGFR stability are still unclear. Here, we'll generate in vivo and in vitro models to pursuit the potential roles and molecular mechanisms of TRB3 in the regulation of tumor progression and drug resistance through stabilizing of EGFR. Our proposed studies may not only provide deep insights in the mechanisms of EGFR stability regulation,but may also provide clues and opportunities for the development of anti-cancer drugs.