{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DEPDC1B is emerging as a multifaceted regulator with critical roles in both normal cell‐cycle dynamics and cancer progression. Functionally, it coordinates the disassembly of focal adhesions and promotes cell de‐adhesion during the G2/M transition by antagonizing RhoA‐based signaling complexes at adhesion sites, thereby facilitating proper mitotic entry."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In several human cancers—including non‐small cell lung cancer, hepatocellular carcinoma, malignant melanoma, bladder cancer, pancreatic ductal adenocarcinoma, and metastatic prostate cancer—as well as in chordoma and canine lymphoma, DEPDC1B is frequently up‐regulated, with its elevated expression correlating with enhanced cell proliferation, migration, invasion, epithelial–mesenchymal transition, and ultimately poorer clinical outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "9"}]}, {"type": "t", "text": " In neuroblastoma, DEPDC1B is up‐regulated downstream of a long noncoding RNA–dependent cascade that increases ERK phosphorylation and stabilizes the oncogenic N‐Myc protein, thereby contributing to tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " In addition, DEPDC1B can act as a guanine nucleotide exchange factor that modulates Rac1 activity, thus promoting cancer cell migration and invasion—a mechanism well illustrated in studies on oral and prostate cancers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "13"}]}, {"type": "t", "text": " Functional knockdown experiments further support its oncogenic role, as reduced DEPDC1B levels lead to cell cycle arrest, increased apoptosis, and diminished tumor growth in vitro and in vivo."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "14"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, by interfacing with multiple signaling pathways—including Wnt/β‐catenin, Akt/GSK3β/Snail, and Rac1–PAK1—DEPDC1B emerges as a convergent hub that not only drives cell cycle progression and de‐adhesion but also orchestrates the migratory and invasive behaviors characteristic of advanced tumors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "20"}]}, {"type": "t", "text": " Collectively, these findings highlight DEPDC1B as a promising diagnostic biomarker and therapeutic target across a wide spectrum of malignancies.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Stefano Marchesi, Francesca Montani, Gianluca Deflorian, et al. 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