Sehgal, M and Nayak, SP and Sahoo, S and Somarelli, JA and Jolly, MK (2024) Mutually exclusive teams-like patterns of gene regulation characterize phenotypic heterogeneity along the noradrenergic-mesenchymal axis in neuroblastoma. In: Cancer Biology and Therapy, 25 (1).
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Abstract
Neuroblastoma is the most frequent extracranial pediatric tumor and leads to 15 of all cancer-related deaths in children. Tumor relapse and therapy resistance in neuroblastoma are driven by phenotypic plasticity and heterogeneity between noradrenergic (NOR) and mesenchymal (MES) cell states. Despite the importance of this phenotypic plasticity, the dynamics and molecular patterns associated with these bidirectional cell-state transitions remain relatively poorly understood. Here, we analyze multiple RNA-seq datasets at both bulk and single-cell resolution, to understand the association between NOR- and MES-specific factors. We observed that NOR-specific and MES-specific expression patterns are largely mutually exclusive, exhibiting a �teams-like� behavior among the genes involved, reminiscent of our earlier observations in lung cancer and melanoma. This antagonism between NOR and MES phenotypes was also associated with metabolic reprogramming and with immunotherapy targets PD-L1 and GD2 as well as with experimental perturbations driving the NOR-MES and/or MES-NOR transition. Further, these �teams-like� patterns were seen only among the NOR- and MES-specific genes, but not in housekeeping genes, possibly highlighting a hallmark of network topology enabling cancer cell plasticity. © 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.
| Item Type: | Journal Article |
|---|---|
| Publication: | Cancer Biology and Therapy |
| Publisher: | Taylor and Francis Ltd. |
| Additional Information: | The copyright for this article belongs to Author. |
| Keywords: | 5 chloro 4 2 (isopropylsulfonyl)phenyl]amino] 2 2 methoxy 4 4 (4 methyl 1 piperazinyl) 1 piperidinylphenylaminopyrimidine; DNA topoisomerase; ganglioside GD2; grhl2; microRNA 200; ovol2; programmed death 1 receptor; topoisomerase 2b; transcription factor Snail; transcription factor Twist; transcription factor ZEB1; unclassified drug, Article; data processing; gene control; gene set enrichment analysis; genetic heterogeneity; housekeeping gene; human; human cell; immunotherapy; information retrieval; k means clustering; neuroblastoma; noradrenergic mesenchymal axis; phenotypic plasticity; principal component analysis; protein expression level; RNA sequencing; SH-SY5Y cell line; signal transduction; transcriptomics; child; gene expression regulation; genetics; pathology; phenotype; tumor recurrence, Child; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Recurrence, Local; Neuroblastoma; Phenotype |
| Department/Centre: | Others |
| Date Deposited: | 01 Mar 2024 09:09 |
| Last Modified: | 01 Mar 2024 09:09 |
| URI: | https://eprints.iisc.ac.in/id/eprint/83970 |
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