Cancer-associated fibroblasts downregulate type I interferon receptor to stimulate intratumoral stromagenesis
Cho C, Mukherjee R, Peck AR, Sun Y, McBrearty N, Katlinski KV, Gui J, Govindaraju PK, Puré E, Rui H, Fuchs SY. Cancer-associated fibroblasts downregulate type I interferon receptor to stimulate intratumoral stromagenesis. Oncogene 2020, 39: 6129-6137. PMID: 32807917, PMCID: PMC7502515, DOI: 10.1038/s41388-020-01424-7.Peer-Reviewed Original ResearchConceptsCancer-associated fibroblastsFibroblast activation proteinType I interferon receptorTumor growthPancreatic ductal adenocarcinoma tumorsInterferon receptorKnockdown of Smad7Human colorectal cancerGrowth of tumorsSA miceColorectal cancerAdenocarcinoma tumorsSolid tumorsIFNAR1 downregulationGenetic ablationTumorsActivation proteinElevated levelsExtracellular matrixInverse correlationMiceStromagenesisIFNAR1IFNAR1 chainFAP levelsActivation of p38α stress-activated protein kinase drives the formation of the pre-metastatic niche in the lungs
Gui J, Zahedi F, Ortiz A, Cho C, Katlinski K, Alicea-Torres K, Li J, Todd L, Zhang H, Beiting D, Sander C, Kirkwood J, Snow B, Wakeham A, Mak T, Diehl J, Koumenis C, Ryeom S, Stanger B, Puré E, Gabrilovich D, Fuchs S. Activation of p38α stress-activated protein kinase drives the formation of the pre-metastatic niche in the lungs. Nature Cancer 2020, 1: 603-619. PMID: 34124690, PMCID: PMC8194112, DOI: 10.1038/s43018-020-0064-0.Peer-Reviewed Original ResearchConceptsPre-metastatic nicheFibroblast activation proteinStress-activated protein kinasePrimary tumor-derived factorsActivation proteinDisseminated malignant cellsNormal cellsActivity of p38Tumor-derived factorsExpression of chemokinesActivation of p38αInactivation of p38Subsequent pulmonary metastasesStimulation of expressionType I interferonProtein kinaseLung infiltrationP38 inhibitorAdjuvant therapyMetastatic diseaseP38α kinasePulmonary metastasesLung metastasesPoor prognosisMetastatic cancer