{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed that IBTK plays a significant pro‐oncogenic role by sustaining Myc‐driven signaling pathways. In pre‐cancerous murine B cells, IBTK expression is upregulated in correlation with Myc levels, and its activity helps prevent apoptosis, thereby promoting cell survival and tumorigenesis. In human B and non-hematopoietic cells, experimental modulation of Myc confirms that IBTK expression is tightly regulated in a Myc-dependent manner, highlighting its critical contribution to maintaining an environment favorable for tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nThe inhibition or loss of IBTK leads to increased apoptosis and modulation of key apoptotic regulators such as MCL-1 and p53. Despite not affecting the proliferation rate of pre-cancerous cells, IBTK deficiency significantly reduces cell viability through enhanced apoptotic processes, an effect that is observed both in a Myc-dependent setting in murine models and in a Myc-independent context in human epithelial cells. This dual functionality underscores IBTK’s importance in the fine-tuning of cell survival pathways during tumor development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, IBTK haploinsufficiency has been shown to remodel the tumor microenvironment in Myc-driven lymphomagenesis. In murine models, partial loss of Ibtk alters the immunophenotype of lymphomas by increasing the proportion of pre-B cells and enhancing tumor angiogenesis through the upregulation of pro-angiogenic and lymphangiogenic factors such as VEGF, MMP-9, CCL2, and VEGFD. This is accompanied by a notable recruitment of tumor-associated macrophages, collectively promoting an environment that supports tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Eleonora Vecchio, Gaetanina Golino, Antonio Pisano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IBTK contributes to B-cell lymphomagenesis in Eμ-myc transgenic mice conferring resistance to apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-019-1557-6"}], "href": "https://doi.org/10.1038/s41419-019-1557-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30975981"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30975981"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Eleonora Vecchio, Giuseppe Fiume, Chiara Mignogna, et al. "}, {"type": "b", "children": [{"type": "t", "text": "IBTK Haploinsufficiency Affects the Tumor Microenvironment of Myc-Driven Lymphoma in E-myc Mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms21030885"}], "href": "https://doi.org/10.3390/ijms21030885"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32019112"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32019112"}]}]}]}