title: Inhibition of Mer and Axl receptor tyrosine kinases leads to increased apoptosis and improved chemosensitivity in human neuroblastoma.
abstract: Ectopic expression of Mer and Axl receptor tyrosine kinases (RTKs) are frequently found in various cancers as known to promote oncogenesis by activating antiapoptotic signaling pathways. However, the roles of these receptors in neuroblastoma remain unclear. We found Mer and Axl was co-expressed in neuroblastoma patient samples and cell lines. Ligand-dependent Mer or Axl activation led to an increase in phosphorylated ERK1/2, AKT and FAK indicating roles for these RTKs in multiple oncogenic processes. Furthermore, Mer and Axl knockdown led to apoptosis and inhibition of migration as well as a significant increase in chemosensitivity in response to cisplatin and vincristine treatment. Taken together, our results demonstrated that inhibition of Mer and Axl improved apoptotic response and chemosensitivity in neuroblastoma, providing new insights into development of novel therapeutic strategies by targeting these oncogenes.
authors.affiliation: Department of Medical Imaging, The Second Hospital of Shandong University, Jinan 250033, China. Electronic address: yixinli2020@163.com.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Orthopedic Surgery, The Second Hospital of Shandong University, Jinan 250033, China.
authors.forename: Xiqian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The Second Hospital of Shandong University, Jinan 250033, China.
authors.forename: Shaojie
authors.initials: S
authors.lastname: Bi
authors.affiliation: Department of Medical Imaging, The Second Hospital of Shandong University, Jinan 250033, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan 250033, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yu
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D055785:Gene Knockdown Techniques; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008024:Ligands; D009447:Neuroblastoma / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014750:Vincristine / Q000494:pharmacology; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
chemical_list: D002945:Cisplatin; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D014750:Vincristine; D000076202:c-Mer Tyrosine Kinase; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C097072:MERTK protein, human; C000722289:AXL protein, human
keywords: Axl; Chemosensitivity; Mer; Receptor tyrosine kinase; Targeted therapy