2. Academic Validation
  3. CAMK2G Promotes Neuronal Differentiation and Inhibits Migration in Neuroblastoma

CAMK2G Promotes Neuronal Differentiation and Inhibits Migration in Neuroblastoma

  • J Pediatr Surg. 2024 Aug 22:161679. doi: 10.1016/j.jpedsurg.2024.08.019.
Yujie Ma 1,  Cong He 2,  Weihong Lin 1,  Jing Wang 1,  Chaoliang Xu 3,  Deshen Pan 3,  Zuopeng Wang 1,  Wei Yao 1,  Rui Dong 1,  Deshui Jia 3,  Kai Li 4
Affiliations

Affiliations

  • 1 Department of Pediatric Surgery, Children's Hospital of Fudan University, National Children's Medical Center, 399 Wanyuan Road, Shanghai 201102, China.
  • 2 Laboratory of Cancer Genomics and Biology, Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 201321, China.
  • 3 Laboratory of Cancer Genomics and Biology, Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
  • 4 Department of Pediatric Surgery, Children's Hospital of Fudan University, National Children's Medical Center, 399 Wanyuan Road, Shanghai 201102, China. Electronic address: likai2727@163.com.
PMID: 39266386 DOI: 10.1016/j.jpedsurg.2024.08.019
Abstract

Purpose: Neuroblastoma (NB) originates from differentiation arrest of sympathoadrenal progenitors in the neural crest. It is necessary to reveal the differentiation mechanism of NB. Previously, we reported that Purkinje cell protein 4 (PCP4) is a well-differentiated marker of NB tissues. Herein, we explored the underlying mechanism of PCP4 induced differentiation in order to find better treatment options for patients.

Methods: We screened the interacting proteins of PCP4 by co-immunoprecipitation (Co-IP) and liquid chromatography-mass spectrometry (LC-MS/MS). Then we investigated the relevance between expression of calmodulin-dependent protein kinase II gamma (CAMK2G) and clinical features using R2 platform. We also explored the function of CAMK2G in NB cells by knockdown and RNA Sequencing.

Results: Here, we verified the binding of PCP4 and Calmodulin (CaM) by Co-IP and identified a target kinase of CaM, CAMK2G, by LC-MS/MS. PCP4 overexpression activates the autophosphorylation of CAMK2G. Patients with high CAMK2G expression had better survival while low CAMK2G was associated with unfavorable clinical features including MYCN-amplification, unfavorable histology, progression and high INSS stage. CAMK2G knockdown inhibited neurite outgrowth and down-regulated neuronal differentiation markers (NF-H, MAP2), yet promoted migration, invasion and proliferation. Gene Ontology (GO) analysis showed that knockdown of CAMK2G downregulated the expression of neuronal differentiation-related genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that knockdown of CAMK2G upregulated the expression of migration-related genes.

Conclusion: These findings indicate that CAMK2G activated by PCP4/CaM complex promotes differentiation and inhibits migration in NB cells.

Level of evidence: Not applicable.

Keywords

CAMK2G; Differentiation; Neuroblastoma; PCP4; Pediatric cancer.

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