RUNX3 Regulates Immune Response and Cell Migration

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R-HSA-8949275
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Pathway
Species
Homo sapiens
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RUNX3-mediated transcription regulates development of immune system cells. RUNX3 is necessary for the development of innate lymphoid cells (ILCs) of ILC1 and ILC3 lineages, which reside in the mucosa and are involved in response to external pathogens. RUNX3 exerts its role in the development of ILC1 and ILC3 lineages by stimulating expression of the RORC (RORgamma) gene, encoding nuclear retinoid-related orphan receptor-gamma (Ebihara et al. 2015).
RUNX3 regulates transcription of integrin genes ITGAL (CD11a) and ITGA4 (CD49d), involved in transendothelial migration of leukocytes during immune and inflammatory responses as well as co-stimulation of T cells (Domniguez-Soto et al. 2005). The RUNX3 splicing isoform p33 lacks the Runt domain and is unable to transactivate integrin genes. The p33 isoform is induced during maturation of monocyte-derived dendritic cells (MDDC), leading to reduced expression of genes involved in inflammatory responses, such as IL8 (interleukin-8) (Puig-Kroger et al. 2010).
RUNX3 positively regulates transcription of the SPP1 (osteopontin) gene, which contributes to invasiveness of pancreatic cancer cells (Whittle et al. 2015).

Literature References
PubMed ID Title Journal Year
20615577 The novel RUNX3/p33 isoform is induced upon monocyte-derived dendritic cell maturation and downregulates IL-8 expression

Puig-Kröger, A, Aguilera-Montilla, N, Martínez-Nuñez, R, Domínguez-Soto, A, Sánchez-Cabo, F, Martín-Gayo, E, Zaballos, A, Toribio, ML, Groner, Y, Ito, Y, Dopazo, A, Corcuera, MT, Alonso Martín, MJ, Vega, MA, Corbí, AL

Immunobiology 2010
26414766 Runx3 specifies lineage commitment of innate lymphoid cells

Ebihara, T, Song, C, Ryu, SH, Plougastel-Douglas, B, Yang, L, Levanon, D, Groner, Y, Bern, MD, Stappenbeck, TS, Colonna, M, Egawa, T, Yokoyama, WM

Nat. Immunol. 2015
26004068 RUNX3 Controls a Metastatic Switch in Pancreatic Ductal Adenocarcinoma

Whittle, MC, Izeradjene, K, Rani, PG, Feng, L, Carlson, MA, DelGiorno, KE, Wood, LD, Goggins, M, Hruban, RH, Chang, AE, Calses, P, Thorsen, SM, Hingorani, SR

Cell 2015
16164020 RUNX3 regulates the activity of the CD11a and CD49d integrin gene promoters

Domínguez-Soto, A, Relloso, M, Vega, MA, Corbí, AL, Puig-Kröger, A

Immunobiology 2005
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