Wang Junxiong, Yang Shuo, Min Li, Zhu Shengtao, Guo Shuilong, Zhang Shutian
Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China.
Front Oncol. 2021 Feb 8;10:589241. doi: 10.3389/fonc.2020.589241. eCollection 2020.
The poor prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is associated with the invasion and metastasis of tumor cells. Epithelial cell transforming 2 (ECT2) is a guanine nucleotide exchange factor (GEF) of the Rho family of GTPases. It has also been reported that upregulation of ECT2 in pancreatic cancer, but the role and mechanism of ECT2 have not been previously determined. We found that ECT2 was significantly elevated in PDAC tissues and cells, correlated with more advanced AJCC stage, distant metastases, and overall survival of patients with PDAC. Inhibition and overexpression tests showed that ECT2 promoted proliferation, migration and invasion , and promoted tumor growth and metastasis . We determined that ECT2 was involved in the post-translational regulation of Grb2. ECT2 inhibited the degradation of Grb2 through deubiquitination. Furthermore, knockdown of ECT2 downregulated EGFR levels by accelerating EGFR degradation. EGF stimulation facilitated the formation of ECT2-Grb2 complex. Overall, our findings indicated that ECT2 could be used as a promising new therapeutic candidate for PDAC.
胰腺导管腺癌（PDAC）患者预后较差与肿瘤细胞的侵袭和转移有关。上皮细胞转化2（ECT2）是Rho家族GTP酶的鸟嘌呤核苷酸交换因子（GEF）。也有报道称胰腺癌中ECT2表达上调，但ECT2的作用和机制此前尚未明确。我们发现ECT2在PDAC组织和细胞中显著升高，与更晚期的美国癌症联合委员会（AJCC）分期、远处转移以及PDAC患者的总生存期相关。抑制和过表达试验表明，ECT2促进增殖、迁移和侵袭，并促进肿瘤生长和转移。我们确定ECT2参与Grb2的翻译后调控。ECT2通过去泛素化抑制Grb2的降解。此外，敲低ECT2可通过加速表皮生长因子受体（EGFR）降解而下调EGFR水平。表皮生长因子（EGF）刺激促进ECT2 - Grb2复合物的形成。总体而言，我们的研究结果表明ECT2有望成为PDAC新的治疗靶点。
