{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTIAM1 is a Rac‐specific guanine nucleotide exchange factor that plays a central role in orchestrating actin cytoskeletal reorganization to promote the formation of lamellipodia, cell spreading, migration, and invasion. In multiple studies, TIAM1‐dependent Rac1 activation was shown to be critical for initiating directed cellular protrusions under the control of upstream signals—including receptor tyrosine kinases, Src, Rap1, and phosphoinositide signals—and for coordinating changes in cell morphology. Notably, TIAM1 has been linked to altered adhesive properties and increased motility in various cancer cells, where its overexpression or mis‐localization contributes to enhanced invasive and metastatic behavior in models of melanoma, colorectal, and other carcinomas."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in stimulating cell motility, TIAM1 functions as an important regulator of cell adhesion and endothelial barrier integrity. By localizing to discrete plasma membrane domains—often via interactions with lipid messengers and scaffolding proteins such as talin, IRSp53, and CD44—TIAM1 facilitates localized Rac1 activation that modulates adherens junction dynamics. These events are critical for both the stabilization of endothelial junctions, which regulates vascular permeability, and for the dynamic disassembly of intercellular contacts during tumor cell invasion."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTIAM1 activity is subject to intricate regulation by post‐transcriptional and post‐translational mechanisms that determine its expression level, subcellular localization, and stability. A number of microRNAs (for example, miR‑10b, miR‑21, miR‑29c, miR‑22, miR‑31 and miR‑141) target TIAM1 to attenuate Rac1 signaling and thereby suppress migration and invasion in various tumor models. Moreover, TIAM1 is modulated by phosphorylation events (including Src‑dependent phosphorylation), deacetylation by SIRT proteins, and targeted degradation by ubiquitin ligases—all of which contribute to the balance between TIAM1‐mediated Rac activation and opposing signals, such as RhoA activity, to ultimately impact tumor progression, chemoresistance, and even immune cell function (for instance, IL‑17 production in Th17 cells). These regulatory mechanisms underline the dual role of TIAM1 in both promoting oncogenic behaviors in multiple cancers (colorectal, gastric, prostate, ovarian, pancreatic and hepatocellular carcinomas) and, in some contexts, restraining pro‐invasive pathways via nuclear functions that antagonize the activity of transcriptional co‑activators such as YAP/TAZ."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "20", "end_ref": "34"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ian N Fleming, Ian H Batty, Alan R Prescott, et al. 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