Department of General Surgery, Central Hospital of Xuhui District, Shanghai, People's Republic of China.
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Med Oncol. 2022 Apr 28;39(5):64. doi: 10.1007/s12032-021-01568-w.
Genomic instability and mutability are a prominent character of tumor. The whole-exosome sequence reveals that ERBB2 mutations are the representative mutations of gallbladder carcinoma, which takes potential targets for gallbladder carcinoma therapy. However, the roles of ERBB2 mutations are unclear in gallbladder carcinoma. We identified S310F mutation is the hottest mutation of ERBB2 mutations from TCGA PanCancer Altas data with 10,967 samples and our previous study with 157 gallbladder carcinoma samples. S310F mutation located in ERBB2 extracellular domain, promoted ERBB2 homodimerization and consequent auto-phosphorylation to activate the downstream PI3K/AKT and MAPK pathways, which was independent on ERBB1, ERBB3, and ERBB4. ERBB2 S310F mutation up-regulated aerobic glycolysis and promoted gallbladder carcinoma growth. Our study reveals the roles of ERBB2 S310F mutation, which is beneficial to ERBB2 S310F mutant gallbladder carcinoma therapy.
基因组不稳定性和突变性是肿瘤的一个显著特征。全外显子组序列揭示， ERBB2 突变是胆囊癌的代表性突变，这为胆囊癌的治疗提供了潜在的靶点。然而， ERBB2 突变在胆囊癌中的作用尚不清楚。我们从 TCGA PanCancer Altas 数据（包含 10967 个样本）和我们之前的 157 个胆囊癌样本研究中鉴定出 S310F 突变是 ERBB2 突变中最热门的突变。S310F 突变位于 ERBB2 的细胞外结构域，促进 ERBB2 同源二聚化，继而导致自身磷酸化，激活下游的 PI3K/AKT 和 MAPK 通路，这一过程独立于 ERBB1、ERBB3 和 ERBB4。 ERBB2 S310F 突变上调有氧糖酵解，促进胆囊癌的生长。我们的研究揭示了 ERBB2 S310F 突变的作用，这有利于 ERBB2 S310F 突变型胆囊癌的治疗。
