LCK regulates apoptosis and intercellular communication networks in neuroblastoma

Neuroblastoma is the most common solid malignancy of childhood with poor prognosis in high-risk patients. The tumor microenvironment, particularly the metastatic bone marrow niche, plays a critical role in disease progression. Lymphocyte-specific protein tyrosine kinase (LCK) is essential for T cell function and implicated in apoptosis induction by anticancer drugs, yet its role in neuroblastoma remains unclear. This study investigated LCK expression changes in neuroblastoma cells following doxorubicin treatment, examined molecular interactions between LCK and doxorubicin, and elucidated LCK's role in the tumor immune microenvironment. Differential LCK expression was analyzed across control, non-metastatic and metastatic neuroblastoma samples using single-cell transcriptomics. CellChat framework mapped immune cell interaction networks. LCK expression was evaluated before and after doxorubicin treatment, and molecular docking assessed direct binding between LCK and doxorubicin. CellChat revealed significantly altered communication between T cells and hematopoietic progenitors in metastatic samples, with increased interactions associated with LCK-expressing cells. Molecular docking suggested a potential interaction between doxorubicin and the LCK kinase domain. Chromosomal localization of LCK at 1p32-35, frequently deleted in aggressive neuroblastomas, underscores its clinical relevance. LCK expression changes were associated with doxorubicin response and apoptosis-related transcriptional changes. These findings suggest LCK as a candidate biomarker for predicting treatment response and a potential target for further investigation in neuroblastoma. Experimental validation is required to establish the functional role of LCK in this context.