{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPLEK2 is a modular protein characterized by two pleckstrin homology (PH) domains and a DEP domain that mediates its association with membrane‐bound phosphatidylinositols generated downstream of PI3K. Early studies in lymphoid and adherent cells demonstrated that PLEK2 localizes to the plasma membrane and cell protrusions where it facilitates actin reorganization and cell spreading. Its ability to bind specifically to D3–D5 phosphoinositides via its PH domains is essential for these cytoskeletal functions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn multiple cancer contexts, PLEK2 is upregulated and contributes to oncogenic processes. In non‐small cell lung cancer (NSCLC) and esophageal squamous cell carcinoma (ESCC), TGF‑β stimulation induces PLEK2 expression via transcription factors such as ELK1, Smad3, and STAT3. Elevated PLEK2 levels then promote epithelial–mesenchymal transition, cell migration, vascular invasion, and chemoresistance. In colorectal, gastric, head and neck, and prostate cancers, aberrant transcriptional activation (for example by BRD4 or by APC/β‑catenin signaling) or loss of AR‐mediated repression elevates PLEK2, which in turn drives cell cycle progression and anti‐apoptotic signaling through downstream effectors including PI3K/AKT. Moreover, PLEK2 has been shown to interact with regulators such as SHIP2 and PPM1B, thereby modulating additional pro‐survival and NF‑κB pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThus, acting at the nexus of cytoskeletal modulation and oncogenic signaling, PLEK2 serves as a critical mediator of cell motility and transformation. Its upregulation in a range of malignancies correlates with poor patient prognosis and aggressive tumor phenotypes, suggesting that PLEK2 not only represents a valuable prognostic marker but also a promising therapeutic target to counteract metastasis and drug resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_fs", "start_ref": "10", "end_ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tami L Bach, Wesley T Kerr, Yanfeng Wang, et al. 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