TIAM1
Overview
TIAM1 (T cell lymphoma invasion and metastasis 1) is a guanine nucleotide exchange factor (GEF) that activates RAC1, promoting cytoskeletal reorganization, cell migration, and invasion. In cancer, TIAM1 is recurrently mutated alongside other RAC1-GEF genes (TRIO, VAV2, ECT2, DOCK2, ELMO1) in esophageal adenocarcinoma (EAC), implicating the RAC1 signaling axis as a driver of tumor invasion.
Alterations observed in the corpus
- Recurrently mutated in EAC (145 tumors; whole-exome sequencing); named as one of several upstream RAC1-regulatory GEFs altered in this cancer type alongside TRIO, VAV2, ECT2, DOCK2, and ELMO1 PMID:23525077.
Cancer types (linked)
- EAC: Part of a recurrently mutated RAC1-GEF axis; RAC1 pathway alterations (across all GEF/effector genes) are enriched in esophageal adenocarcinoma PMID:23525077.
Co-occurrence and mutual exclusivity
- Co-altered with TRIO, VAV2, ECT2, DOCK2, and ELMO1 as upstream regulators of RAC1 in EAC; downstream effector PAK1 is recurrently amplified at 11q13 in the same tumors PMID:23525077.
Therapeutic relevance
- RAC1 pathway activation across multiple GEF genes in EAC nominates this axis for therapeutic investigation, though no specific TIAM1-targeting agents are reported in the corpus PMID:23525077.
Open questions
- Functional validation of TIAM1 mutations in EAC (invasion assays equivalent to those performed for ELMO1) has not yet been reported PMID:23525077.
Sources
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