Watch PAPS' Dr. Yujie Ma's presentation on “CAMK2G Promotes Neuronal Differentiation and Inhibits Migration in Neuroblastoma” at the 2025 Best of the Best in Pediatric Surgery event!
Moderators: Drs. Todd Ponsky, Dan von Allmen, and Meera Kotagal
Type: video · 8 min · posted 2025-03-19 Canonical: https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036 ## Chapters - [0:00](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=0) Introduction - [0:30](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=30) Background and Mechanism - [2:54](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=174) Clinical Relevance and Functional Studies - [4:42](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=282) Conclusions - [5:24](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=324) Discussion with Dr. Erin Brown ## Statements - "Neuroblastoma is the most common extracranial solid tumor of childhood arising from aberrant differentiation of sympatho adrenal cells in neuro crest" — Yujie Ma (epidemiological) [0:45](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=45) - "Retinoic acid is used to induce differentiation in treatment of high risk neuroblastoma" — Yujie Ma (guideline) [0:56](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=56) - "Retinoic acid efficacy varied in patients due to the highly heterogeneity of this disease" — Yujie Ma (clinical) [1:03](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=63) - "PCP4 was identified as one of the differentiation markers of neuroblastoma tumor cells in a previous Cancer Cell publication" — Yujie Ma (clinical) [1:19](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=79) - "PCP4 modulates the rate of calcium binding to calmodulin, which is a critical step in activating calmodulin dependent kinase" — Yujie Ma (clinical) [1:38](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=98) - "The binding of PCP4 with calmodulin was verified in neuroblastoma by co-immunoprecipitation" — Yujie Ma (clinical) [1:49](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=109) - "CAMK2G was identified as a target kinase of calmodulin using mass spectrometry" — Yujie Ma (clinical) [1:49](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=109) - "CAMK2G is a member of the serine threonine protein kinase family" — Yujie Ma (clinical) [2:06](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=126) - "CAMK2G plays an important role in neuronal development and synaptic plasticity" — Yujie Ma (clinical) [2:10](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=130) - "When CAMK2G is activated by calmodulin, it gets autophosphorylated at the site of threonine 287" — Yujie Ma (clinical) [2:24](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=144) - "PCP4 overexpression upregulated the threonine 287 phosphorylation of CAMK2G in neuroblastoma cells" — Yujie Ma (clinical) [2:33](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=153) - "Low CAMK2G mRNA expression was associated with worse overall and event-free survival" — Yujie Ma (clinical) [3:02](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=182) - "Low CAMK2G expression was associated with advanced INSS stages and unfavorable histology" — Yujie Ma (clinical) [3:02](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=182) - "Low CAMK2G expression was associated with MYCN amplified status, high risk, and tumor progression" — Yujie Ma (clinical) [3:14](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=194) - "CAMK2G knockdown in SKNSH cells resulted in inhibited neuron outgrowths even under the induction of retinoic acid" — Yujie Ma (clinical) [3:30](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=210) - "Expression of neuronal differentiation markers were down regulated following CAMK2G knockdown" — Yujie Ma (clinical) [3:44](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=224) - "CAMK2G knockdown promoted migration and invasion of neuroblastoma cells as shown by transwell assays" — Yujie Ma (clinical) [4:13](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=253) - "CAMK2G expression is associated with favorable clinical features" — Yujie Ma (clinical) [4:42](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=282) - "CAMK2G plays an essential role in promoting neuronal differentiation and inhibiting migration in neuroblastoma" — Yujie Ma (clinical) [4:51](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=291) - "CAMK2G is expressed low in SKNSH cells" — Yujie Ma (clinical) [6:20](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=380) - "CAMK2G is highly expressed in BE2 and SKNS cell lines, which are MYCN amplified cell lines" — Yujie Ma (clinical) [6:33](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=393) - "CAMK2G function is not strong enough to overcome the oncogenic function of MYCN" — Yujie Ma (clinical) [7:11](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=431) - "CAMK2G did not regulate neuronal differentiation in MYCN amplified cell lines" — Yujie Ma (clinical) [7:11](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=431) - "The CAMK2G mechanism is not universal for all neuroblastoma cell lines and patients" — Yujie Ma (opinion) [7:40](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=460) - "The CAMK2G mechanism can only be explained in MYCN non-amplified cell lines and the corresponding patients" — Yujie Ma (opinion) [7:45](https://library.globalcastmd.com/watch/dr-yujie-ma-best-of-the-best-in-pediatric-surgery-2025-10036?t=465) ## Transcript All right. So, um, we're gonna go on to the next heat. Um, and, uh, so now we're gonna be having, uh, paps and caps, uh, going head to head here. Um, so the first presentation, uh, is Doctor Yuli Ma, uh, and it's CAMK2G promotes neuronal differentiation and inhibits migration in neuroblastoma. And, uh, Yuli comes from Children's Hospital of Fudan University in China. Thank you for your very kind introduction. I'd like to take this opportunity to present our work of CAMK2G promote neuronal differentiation and inhibits migration in neuroblastoma. Neuroblastoma is the most common extracranial solid tumor of childhood arising from aberrant differentiation of sympatho adrenal cells in neuro crest. Retinoic acid is used to induce differentiation in treatment of high risk neuroblastoma. However, its efficacy varied in patients due to the highly heterogeneity of this disease. Therefore, identifying the novel differentiation mechanism is of great importance to develop effective therapy. Our previous publication in cancer cell has identified PCP4 as one of the differentiation markers of neuroblast tumor tumor cells. So in this study, we aim to explore the underlying mechanism in order to find better treatment options for patients. Functionally, PCP4 modulates the rate of calcium binding to camodulin, which is a critical step in activating camodulin dependent kinase. Here, we verified in neuroblastoma, the binding of PCP4 with CAMmodulin by co-immunoprecipitation, and using mass spectrometry, we identified a target kindness of CAMmodulin, CAMK2G. CaMK2G is a member of the sorri thrilling protein kinase family. It plays an important role in neuronal development and the synaptic plasticity, which is similar to that of PCP4, but its function in neuroblastoma has been largely uncharacterized. When it is activated by chemodulin, it gets autophosphorylated at the site of thrilling 287. Here, we show that PCP4 overexpression upregulated the thrilling 287 phosphorylation of chem K2G in neuroblastoma cells. These results lead us to hypothesize that PCP4 may affect neuroblastoma differentiation by activating chem K2G. So next, we investigate the clinical relevance of chem K2G expression with the help of R2 platform. We found that low cam K2g mRNA expression was associated with worse overall and event-free survival, advanced INSS stages, and unfavorable histology. As well as Make an amplified status, high risk, and tumor progression. This results indicated the tumor suppressor role of chemK2G in neuroblastoma tumorrigenesis. To explore the function of chem K2G in neuroblastoma, we knocked down chem K2G in SKNSH cells, and we observed inhibited neuron outgrowths even under the induction of retinoic acid. And expression of neuronal differentiation markers were also down regulated following chem K2G knockdown. These changes were further verified transcriptionally by RNA sequencing. Geo enrichment analysis conducted in the down regulated genes show that enriched terms were related to neuronal differentiation, such as synaptic signaling, plasma membrane, and I channel activity. Yeah, Macdonal cam K2G also promote migration and invasion of neuroblastoma cells as shown by transwe essays. And KEGG analysis in upregulated genes identified enriched pathways mainly associated with tumor migration and invasion, such as extracellular matrix receptor interaction, focal adhesion, and the regulation of acting psychoskeleton. So, in conclusion, in this study, we found chem K2G expression is associated with favorable clinical features. We highlighted the essential role of chem K2G in promoting neuronal differentiation and inhibiting migration in neuroblastoma. Future studies are needed to look for ACO proteins, which are upregulated, activated, or blocked from degradation in chem K2G low expressed neuroblastoma tumors, so that we can put up with novel therapeutic strategies. Thank you for your attention. I'd like to take any questions. Perfect. Thank you so much for the paper and um thanks for joining us. Uh, in the, I don't know what time is it there right now? It's in the evening, 10 o'clock. Thank you. Um, so, um, Mira, do you wanna introduce Doctor Brown? Yeah, so we're excited to have Doctor Erin Brown join us. She's an associate professor of surgery at UC Davis and does both clinical and, uh, research focused on neuroblastoma. Hi, everybody. How are you? Great presentation, Doctor Moth. Thank you. Uh, my question for you is, how universal is this down-regulation of CAMK2G across neuroblastoma cells? As you mentioned, it's really heterogeneous, and so that's a problem when developing these targeted therapies. So how, how are you seeing this across different neuroblastoma cell lines? Oh well, we test the expression of chem K2G in multiple neuroblastoma cell lines and uh it's rarely, it's expressed the low in the SKNSH cells. That's why we overexpress PCP4, sorry, overexpressed the chem K2G in this cell line and In other cellulites such as BE2 SKNS, it's, it is highly expressed, uh, but the in this cell lines were MYC and amplified cell lines and uh during the study we found that the CAAMK2G, its function is not that strong to uh overcome the uh oncogen function of ACN. Uh, Camp K2G, uh, didn't uh regulate the neuronal differentiation in these cell lines. So, Um, So I think uh this is. Sorry. That's OK. Keep going. Uh, it's hard to speak in English. Um, uh, so, uh, I think, uh, this mechanism is uh. Not universal for all the neuroblastoma cell line and patients. Uh, it can only be explained in a non-amplified cell lines and the, the corresponding patients. Thank you, Doctor Ma. Thank you so much. Very well presented. Thank you. Beautiful paper. Beautiful presentation. I see why they, uh, chose your paper. So thanks for the presentation. Just stick around and, um, if there's any questions, uh, we'll send them to you. --- Not medical advice · citation policy: https://library.globalcastmd.com/ai