Role of Yes-associated protein 1 in gliomas: pathologic and therapeutic aspects.
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.
Fourth Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou, 061001, China, liu_yc007@hotmail.com.
Yong-Chang
YC
Liu
Yan-zhou
YZ
Wang
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D000090683:Hippo Signaling Pathway; D006801:Humans; D014411:Neoplastic Stem Cells / Q000473:pathology; D025581:Neurofibromin 2 / Q000235:genetics; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D025581:Neurofibromin 2; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D017346:Protein Serine-Threonine Kinases