近日上海肿瘤研究所李宗海研究员领导的肿瘤生物治疗研究组在肿瘤生物治疗新靶点的发现与验证研究领域中获新的研究进展。相关研究成果发表在最新一期的《肿瘤形成》（Neoplasia）杂志上。
李宗海研究员早年毕业于湖南医科大学，2005年进入上海肿瘤研究所担任癌基因及相关基因国家重点实验室生物治疗研究组长。长期从事肿瘤生物治疗研究，承担国家“十一五”科技重大专项、“973”、国家自然科学基金面上项目、上海市科委重大及重点科技攻关项目等课题。在FASEB J, J Biol Chem, Neoplasia, Cancer Immunoloy Immunotherapy, Cancer lett, BioTechniques等杂志发表论文四十多篇。
表皮生长因子受体(EGFR)信号转导途径在肿瘤细胞的增殖、损伤修复、侵袭及新生血管形成等方面起重要作用。近年来靶向EGFR药物已成为肿瘤治疗的新热点。全球目前已经有四个针对EGFR靶向药物（Cetuximab, Panitumumab, Gefitinib, Erlotinib）用于临床肿瘤治疗，前景看好。
继今年初研制出具有自主知识产权的表皮生长因子受体III型变异体单克隆抗体后，该研究组在表皮生长因子受体研究领域近期又获得了新的发现。博士研究生王海等人在李宗海老师的指导下最近在研究中发现了一种新的表皮生长因子受体变异体(de4 EGFR)，该变异体在一些脑胶质瘤、卵巢癌和前列腺癌中有表达，而在所检测的相应癌旁组织中没有表达，研究还发现该变异体可显著促进脑胶质瘤转移。
目前该课题组已将该变异体申报了国家发明专利，有望成为有自主知识产权的肿瘤治疗新靶点。(生物谷 Bioon.com)
生物谷推荐原文出处：
Neoplasia
Identification of an Exon 4-Deletion Variant of Epidermal Growth Factor Receptor with Increased Metastasis-Promoting Capacity1,2
Hai Wang, Min Zhou,Bizhi Shi,Qingli Zhang,Hua Jiang, Yinghao Sun, Jianhua Liu, Keke Zhou,Ming Yao, Jianren Gu,Shengli Yang, Ying Mao,and Zonghai Li
Several types of epidermal growth factor receptor (EGFR) gene alternations have been observed in human tumors. Here we present a novel EGFR variant with aberrant splicing of exon 4 (named as de4 EGFR). Variant-specific polymerase chain reaction showed that de4 EGFR was expressed in some glioma (4/40), prostate cancer (3/11), and ovarian cancer (3/9) tissues but not in tissues adjacent to tumors or normal tissues. de4 EGFR displayed an enhanced transformation and a higher metastasis-promoting capacity in comparison to wild-type EGFR. With minimal EGF-binding activity, de4 EGFR underwent ligand-independent autophosphorylation and self-dimerization. Moreover, in serum-starved condition, de4 EGFR expression in U87 MG cells significantly upregulated the extracellular signal-regulated kinase and AKT phosphorylation and expression of JUN and Src. Importantly, E-cadherin expression was barely detectable in the U87 MG cells expressing de4 EGFR and restored expression of E-cadherin in these cells inhibited their metastatic behaviors. Taken together, we identified a novel EGFR variant with increased metastasis-promoting activity that may become a promising new target for cancer therapy.
