<br>CD97 (ADGRE5) 在胶质母细胞瘤中的表达谱和致瘤机制使其成为可靶向的脆弱性,Cell Reports

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CD97 (ADGRE5) 在胶质母细胞瘤中的表达谱和致瘤机制使其成为可靶向的脆弱性
Cell Reports ( IF 7.5 ) Pub Date : 2023-11-08 , DOI: 10.1016/j.celrep.2023.113374
Niklas Ravn-Boess ₁ , Nainita Roy ₂ , Takamitsu Hattori ₃ , Devin Bready ₁ , Hayley Donaldson ₁ , Christopher Lawson ₁ , Cathryn Lapierre ₁ , Aryeh Korman ₄ , Tori Rodrick ₄ , Enze Liu ₅ , Joshua D Frenster ₁ , Gabriele Stephan ₁ , Jordan Wilcox ₁ , Alexis D Corrado ₃ , Julia Cai ₁ , Rebecca Ronnen ₁ , Shuai Wang ₁ , Sara Haddock ₁ , Jonathan Sabio Ortiz ₁ , Orin Mishkit ₆ , Alireza Khodadadi-Jamayran ₇ , Aris Tsirigos ₇ , David Fenyö ₈ , David Zagzag ₉ , Julia Drube ₁₀ , Carsten Hoffmann ₁₀ , Fabiana Perna ₁₁ , Drew R Jones ₄ , Richard Possemato ₁₂ , Akiko Koide ₁₃ , Shohei Koide ₃ , Christopher Y Park ₁₂ , Dimitris G Placantonakis ₁₄

Affiliation

Department of Neurosurgery, NYU Grossman School of Medicine, New York, NY 10016, USA.
Department of Pathology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Metabolomics Laboratory, NYU Grossman School of Medicine, New York, NY 10016, USA.
Department of Medicine, Division of Hematology/Oncology, Indiana University, Indianapolis, IN 46202, USA.
Preclinical Imaging Laboratory, NYU Grossman School of Medicine, New York, NY 10016, USA.
Applied Bioinformatics Laboratories, NYU Grossman School of Medicine, New York, NY 10016, USA.
Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA; Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA.
Department of Neurosurgery, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Pathology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Institute for Molecular Cell Biology, Universitätsklinikum Jena, 07745 Jena, Germany.
Moffitt Cancer Center, Tampa, FL 33612, USA.
Department of Pathology, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA.
Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.
Department of Neurosurgery, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Kimmel Center for Stem Cell Biology, NYU Grossman School of Medicine, New York, NY 10016, USA; Brain and Spine Tumor Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Neuroscience Institute, NYU Grossman School of Medicine, New York, NY 10016, USA.

胶质母细胞瘤（GBM）是最常见和最具侵袭性的原发性脑恶性肿瘤。粘附 G 蛋白偶联受体 (aGPCR) 因其作为治疗靶点的潜力而引起了人们的兴趣。在这里，我们证明 CD97 (ADGRE5) 是 GBM 中最有前途的 aGPCR 靶点，因为与健康脑组织相比，它的表达水平更高。 CD97 敲低或敲除显着降低了患者来源的 GBM 培养物 (PDGC) 和的肿瘤起始能力。我们发现 CD97 通过丝裂原激活蛋白激酶 (MAPK) 途径促进糖酵解代谢，该途径依赖于其 C 末端的磷酸化和 β-抑制蛋白的募集。我们还证明 THY1/CD90 可能是 GBM 中的 CD97 配体。最后，我们证明抗 CD97 抗体-药物缀合物选择性杀死肿瘤细胞。我们的研究确定 CD97 是肿瘤代谢的调节剂，阐明了受体激活和信号转导的机制，并为开发靶向 GBM 的生物制剂提供了强有力的科学依据。

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更新日期：2023-11-08

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