Molecular mechanism of pancreatic ductal adenocarcinoma: The heterogeneity of cancer-associated fibroblasts and key signaling pathways

Table 1 Characteristics and functions of cancer-associated fibroblasts subtypes

Types	Origin	Markers	Role in TME
MyCAFs	Pancreatic cells, PSCs	α-SMA, FAP, SMA, PDGFβ	Facilitate tumor cell invasion, migration, drug resistance[23-27]
ICAFs	Bone marrow-originated monocytes	IL-6, IL-1β	Promote tumor inflammation, immune evasion, tumor progression[25,26,33,34]
ApCAFs	Mesenchymal cells	MHC-II, RORγt	Enhance tumor aggression, amplify immune checkpoint inhibitor efficacy[25,35,36]

MyCAF: Myofibroblast-like cancer-associated fibroblast; ICAF: Inflammatory cancer-associated fibroblast; ApCAF: Antigen-presenting cancer-associated fibroblast; PSC: Pancreatic stellate cell; TME: Tumor microenvironment.

Table 2 Key signaling pathways in pancreatic cancer: Main functions and impacts

Signaling pathway	Main function	Impact on pancreatic cancer
TGF-β	Regulates cell proliferation, differentiation, and apoptosis	Initially inhibits tumor cell proliferation, later promotes tumor cell proliferation and metastasis, regulates ECM composition and remodeling, affects chemotherapy efficacy[38-44]
Hedgehog (Hh)	The growth of the pancreas	Promotion of Hh signaling in CAFs, inhibition of Hh signaling can induce apoptosis, suppress cell proliferation, and increase sensitivity to chemotherapeutic agents[45-49]
Wnt/β-catenin	Promotion of the expression of tumorigenic factors	Promotes cancer cell proliferation and growth, regulates ECM remodeling, affects drug resistance[57-60]
JAK/STAT	Cell survival, proliferation, and invasion	Supports tumor cell survival and invasion; enhances the secretory capacity of CAFs; affects drug resistance[26,43,61-64,66,67]

ECM: Extracellular matrix; CAF: Cancer-associated fibroblasts.