iCAF signaling in PDAC

Pathway ID: SIGNOR-IAIP

Description: In contrast to myCAFs, a subpopulation of αSMA-low CAFs with high IL6 secretion was observed distant from tumour epithelium and from myCAFs [56]. This subpopulation was activated by paracrine signalling from tumour cells as demonstrated in a Transwell system (which allows paracrine interactions between organoids and PSCs but blocks direct contact between the two cell types). Single-cell transcriptome analysis revealed upregula- tion of cytokines (IL6, IL11, LIF) and chemokines (CXCL1, CXCL2) in this subpopulation and they were therefore termed inflammatory CAFs (iCAFs) (Figure 1). Gene set enrichment analysis identified upregulation of inflammatory signalling pathways such as IFNγ response, TNF/NFκB, IL2/STAT5, IL6/JAK/STAT3, and the complement pathway in iCAFs in human PDAC . Exploring the Biology of Cancer-Associated Fibroblasts in Pancreatic Cancer. Bryce AS, Dreyer SB, Froeling FEM, Chang DK. Cancers (Basel). 2022 Oct 28;14(21):5302. doi: 10.3390/cancers14215302. PMID: 3635872

Curated by: Marta Iannuccelli

41 Seed Entities

Organism:
Name Primary ID
IL1RL1 Q01638
IL10 P22301
IL10RA Q13651
JAK3 P52333
IL1RAP Q9NPH3
CXCL8 P10145
IL6R P08887
NfKb-p65/p50 SIGNOR-C13
Metastasis SIGNOR-PH107
CCL2 P13500
LIF P15018
IL2RG P31785
CSF1R P07333
IL6ST P40189
Proliferation SIGNOR-PH4
CXCL2 P19875
CXCL1 P09341
Neutrophil_activation SIGNOR-PH211
CXCL3 P19876
Inflammation SIGNOR-PH12
MAP3K7 O43318
CSF1 P09603
AXL P30530
IL1R1 P14778
IL11 P20809
IL34 Q6ZMJ4
IL33 O95760
TNF P01375
JAK1 P23458
M2_polarization SIGNOR-PH55
Epithelial-mesenchymal_transition SIGNOR-PH45
IL2 P60568
CXCR2 P25025
IL2RB P14784
ERK1/2 SIGNOR-PF1
STAT5A P42229
IL1B P01584
STAT3 P40763
IL1A P01583
IL6 P05231
GAS6 Q14393