BCAP31 drives TNBC development by modulating ligand-independent EGFR trafficking and spontaneous EGFR phosphorylation
BCAP31 drives TNBC development by modulating ligand-independent EGFR trafficking and spontaneous EGFR phosphorylation
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BCAP31 通过调节配体独立的 EGFR 运输和自发 EGFR 磷酸化来驱动 TNBC 的发展
DOI：
10.7150/thno.35383
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发表时间：
2019-01-01
期刊：
影响因子：
12.4
通讯作者：
Jin, Wei
中科院分区：
文献类型：
--
作者：
Fu, Wenyan;Sun, Hefen;Jin, Wei
鉴定三阴性乳腺癌（TNBC）的新靶点是一项紧迫的任务，因为靶向治疗延长了雌激素受体+/孕激素受体+和HER 2+癌症患者的寿命。研究方法：参与内质网中蛋白质加工的基因（已报道其在癌症中起关键作用）用于功能丧失筛选以评价这些基因的致癌作用，从而鉴定TNBC中的候选靶基因。体外和体内功能测定以及临床预后分析被用来研究该基因的致癌作用。分子和细胞为基础的分析，进一步研究的机制。结果如下：B细胞受体相关蛋白31（BCAP 31）是一种癌基因，其表达与患者的早期复发和不良生存率相关。体外研究进一步表明，BCAP 31通过促进TNBC发展而作为关键癌基因发挥作用。我们还表明，BCAP 31与表皮生长因子受体（EGFR）相互作用，并作为配体非依赖性EGFR再循环的抑制剂，维持EGFR自磷酸化和下游信号转导的激活。结论：这些发现揭示了ER相关蛋白BCAP 31在EGFR失调和TNBC发展中的功能作用。
Identification of novel targets for triple-negative breast cancer (TNBC) is an urgent task as targeted therapies have increased the lifespans of Oestrogen Receptor +/ Progesterone Receptor + and HER2+ cancer patients. Methods: genes involved in protein processing in the endoplasmic reticulum, which have been reported to be key players in cancer, were used in loss-of-function screening to evaluate the oncogenic roles of these genes to identify candidate target genes in TNBC. In vitro and in vivo function assays as well as clinical prognostic analysis were used to study the oncogenic role of the gene. Molecular and cell based assays were further employed to investigate the mechanisms. Results: B Cell Receptor Associated Protein 31 (BCAP31), the expression of which is correlated with early recurrence and poor survival among patients, was identified an oncogene in our assay. In vitro studies further suggested that BCAP31 acts as a key oncogene by promoting TNBC development. We also showed that BCAP31 interacts with epidermal growth factor receptor (EGFR) and serves as an inhibitor of ligand-independent EGFR recycling, sustaining EGFR autophosphorylation and activation of downstream signalling. Conclusion: These findings reveal the functional role of BCAP31, an ER-related protein, in EGFR dysregulation and TNBC development.