
-   High Egr-1 expression was associated with improved patient survival and inhibited colon cancer cell proliferation, migration and invasion. Egr1 inhibits colon cancer cell proliferation, migration and invasion via regulating CDKL1 at the transcriptional level [PMID: 34165179]. Meanwhile, EGR-1 also increase expression of NAG-1 [PMID: 23220538]. The expression of NAG-1 inhibits the development of intestinal tumors in animal models [PMID: 17101328, PMID: 19401523].
-   EGR1 is a novel target for AhR agonists in human lung epithelial cells. The increase in EGR1 expression in pulmonary epithelial cells appears to be mediated through a post-transcriptional mechanism that leads to the higher EGR1 protein levels in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polycyclic aromatic hydrocarbons (PAHs) treated cells, compared to vehicle treated cells [PMID: 15342960].
-   EGR-1 seems to play a critical role in myocardial reperfusion injury because downregulation of EGR-1 either by Postcon or the use of pharmacological intervention reduces infarct size, most likely through an inhibition of inflammation-mediated processes [PMID: 24365880].
-   Transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFbeta1, PTEN, p53 and fibronectin. Egr1-null cells were found to be insensitive to genotoxic stress and do not arrest following DNA damage. Egr1 directly induces the transcription of p53. p53 controls the expression of the cell cycle inhibitor p21 which also regulated by Egr1 through direct induction of TGFbeta1. Binding of p53 promoter by Egr-1 may lead to cell cycle arrest, senescence, and for cells that survive "crisis"-transformation [PMID: 16138117].
-   Transcription factor Egr1 induces expression of NHE2, a Na(+)/H(+) exchanger (NHEs) that play important roles in regulating internal pH (pHi), cell volume and neutral Na(+) absorption in the human intestine [PMID: 24376510]

## Summary

In colon diseases and toxicities, EGR1 dysregulation occurs as a response to cellular stress, with its regulation of cell survival, proliferation, and death mechanisms being key [CS: 9]. For instance, in colon cancer, low EGR1 expression correlates with poor prognosis, while its overexpression hampers cancer cell proliferation, migration, and invasion [CS: 8]. This effect is partly due to EGR1's role in activating tumor suppressor genes like TGFbeta1, PTEN, p53, and fibronectin [CS: 7]. Specifically, EGR1-driven p53 activation instigates cell cycle arrest, thereby halting the proliferation of damaged cells and impeding cancer progression [CS: 8].

In inflammatory bowel diseases, EGR1 is upregulated in response to inflammatory triggers, such as TNF-alpha [CS: 8]. This upregulation enhances binding to promoters of genes like mPGES-1, which plays a role in inflammation and pain response [CS: 7]. Moreover, EGR1's regulation extends to the Na(+)/H(+) exchanger (NHE2), important in maintaining pH balance and cell volume in the intestine [CS: 6].
