ELMO1

Overview

ELMO1 (Engulfment and Cell Motility 1) encodes an adaptor protein that partners with DOCK2 to act as a bipartite RAC1 guanine nucleotide exchange factor (GEF), regulating actin cytoskeleton dynamics and cell invasion. In esophageal adenocarcinoma (EAC), ELMO1 is a significantly mutated gene with a recurrent hotspot mutation (p.K312), and EAC-derived mutants have been functionally validated to increase cellular invasion.

Alterations observed in the corpus

  • Significantly mutated in EAC with a recurrent hotspot p.K312 mutation observed in 3 tumors; additional EAC-derived mutants (p.F59L, p.K312E, p.K312T, p.K349R, p.T421N) increase NIH/3T3 invasion 2–7-fold over wild-type in a matrigel transwell assay; wild-type ELMO1 itself increased invasion 7-fold over GFP control (P=0.0040) PMID:23525077

Cancer types (linked)

  • EAC: Significantly mutated gene; recurrent p.K312 hotspot; EAC-derived mutants functionally validated to promote invasion PMID:23525077

Co-occurrence and mutual exclusivity

  • Partners with DOCK2 (RAC1 GEF dimerization partner) in the RAC1 signaling pathway; co-altered with ECT2, TRIO, TIAM1, and VAV2 as upstream RAC1 GEF regulators in EAC; downstream effector PAK1 recurrently amplified at 11q13 PMID:23525077

Therapeutic relevance

  • Functional validation of ELMO1 EAC mutants as pro-invasive suggests the ELMO1-DOCK2-RAC1-PAK1 axis as a potential therapeutic target in EAC.

Open questions

  • Whether specific ELMO1 mutations (e.g., p.K312E vs. p.K312T) have differential pro-invasive activity remains to be characterized.

Sources

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