Liu Yong-Chang, Wang Yan-zhou
Fourth Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou, 061001, China,
Tumour Biol. 2015 Apr;36(4):2223-7. doi: 10.1007/s13277-015-3297-2. Epub 2015 Mar 7.
The activation of proline-rich phosphoprotein Yes-associated protein 1 (YAP1) possesses a possible link between stem/progenitor cells, organ size, and cancer. YAP1 has been indicated as an oncoprotein, and overexpression of YAP1 is reported in many human brain tumors, including infiltrating gliomas. During normal brain development, the neurofibromatosis 2 (NF2) protein suppresses YAP1 activity in neural progenitor cells to promote guidepost cell differentiation, but loss of NF2 causes elevating YAP1 activity in midline neural progenitors, which disrupts guidepost formation. Overexpression of endogenous CD44 (cancer stem cell marker) promotes phosphorylation/inactivation of NF2, and upregulates YAP1 expression and leads to cancer cell resistance in glioblastoma. The hippo pathway is also related to the YAP1 action. However, the mechanism of YAP1 action in glioma is still far from clear understanding. Advances in clinical management based on an improved understanding of the function of YAP1 may help to serve as a molecular target in glioma therapeutics. Knockdown of YAP1 by shRNA technology has been shown to reduce glioma in vitro; however, clinical implications are still under investigation. YAP1 can be used as a diagnostic marker for gliomas to monitor the disease status and may help to evaluate its treatment effects. More functional experiments are needed to support the direct roles of YAP1 on gliomas at molecular and cellular levels.
富含脯氨酸的磷酸化蛋白Yes相关蛋白1（YAP1）的激活在干细胞/祖细胞、器官大小和癌症之间可能存在联系。YAP1已被表明是一种癌蛋白，在许多人类脑肿瘤中都有YAP1过表达的报道，包括浸润性胶质瘤。在正常脑发育过程中，神经纤维瘤病2（NF2）蛋白抑制神经祖细胞中YAP1的活性，以促进路标细胞分化，但NF2的缺失会导致中线神经祖细胞中YAP1活性升高，从而破坏路标形成。内源性CD44（癌症干细胞标志物）的过表达促进NF2的磷酸化/失活，并上调YAP1表达，导致胶质母细胞瘤中的癌细胞耐药。河马通路也与YAP1的作用有关。然而，YAP1在胶质瘤中的作用机制仍远未明确。基于对YAP1功能的更好理解而在临床管理方面取得的进展可能有助于作为胶质瘤治疗的分子靶点。通过shRNA技术敲低YAP1已被证明可在体外减少胶质瘤；然而，其临床意义仍在研究中。YAP1可作为胶质瘤的诊断标志物来监测疾病状态，并可能有助于评估其治疗效果。需要更多的功能实验来支持YAP1在分子和细胞水平上对胶质瘤的确切作用。
