| http://purl.uniprot.org/citations/35962191 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35962191 | http://www.w3.org/2000/01/rdf-schema#comment | "Tumor cell dependence on activated oncogenes is considered a therapeutic target, but protumorigenic microenvironment-mediated cellular addiction to specific oncogenic signaling molecules remains to be further defined. Here, we showed that tumor-associated macrophages (TAMs) produced an abundance of C-C motif chemokine 22 (CCL22), whose expression in the tumor stroma was positively associated with the level of intratumoral phospho-focal adhesion kinase (pFAK Tyr397), tumor metastasis and reduced patient survival. Functionally, CCL22-stimulated hyperactivation of FAK was correlated with increased malignant progression of cancer cells. CCL22-induced addiction to FAK was demonstrated by the persistent suppression of tumor progression upon FAK-specific inhibition. Mechanistically, we identified that diacylglycerol kinase α (DGKα) acted as a signaling adaptor to link the CCL22 receptor C-C motif chemokine receptor 4 (CCR4) and FAK and promoted CCL22-induced activation of the FAK/AKT pathway. CCL22/CCR4 signaling activated the intracellular Ca2+/phospholipase C-γ1 (PLC-γ1) axis to stimulate the phosphorylation of DGKα at a tyrosine residue (Tyr335) and promoted the translocation of DGKα to the plasma membrane to assemble the DGKα/FAK signalosome, which critically contributed to regulating sensitivity to FAK inhibitors in cancer cells. The identification of TAM-driven intratumoral FAK addiction provides opportunities for utilizing the tumor-promoting microenvironment to achieve striking anticancer effects."xsd:string |
| http://purl.uniprot.org/citations/35962191 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41423-022-00903-z"xsd:string |
| http://purl.uniprot.org/citations/35962191 | http://purl.uniprot.org/core/author | "Chen J."xsd:string |
| http://purl.uniprot.org/citations/35962191 | http://purl.uniprot.org/core/author | "Wang Y."xsd:string |
| http://purl.uniprot.org/citations/35962191 | http://purl.uniprot.org/core/author | "Xiao Y."xsd:string |
| http://purl.uniprot.org/citations/35962191 | http://purl.uniprot.org/core/author | "Zhang J."xsd:string |
| http://purl.uniprot.org/citations/35962191 | http://purl.uniprot.org/core/author | "Zhang L."xsd:string |
| http://purl.uniprot.org/citations/35962191 | http://purl.uniprot.org/core/author | "Wu Q."xsd:string |
| http://purl.uniprot.org/citations/35962191 | http://purl.uniprot.org/core/author | "Zhao D."xsd:string |
| http://purl.uniprot.org/citations/35962191 | http://purl.uniprot.org/core/author | "Zhan Q."xsd:string |
| http://purl.uniprot.org/citations/35962191 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/35962191 | http://purl.uniprot.org/core/name | "Cell Mol Immunol"xsd:string |
| http://purl.uniprot.org/citations/35962191 | http://purl.uniprot.org/core/pages | "1054-1066"xsd:string |
| http://purl.uniprot.org/citations/35962191 | http://purl.uniprot.org/core/title | "Tumor-associated macrophage (TAM)-derived CCL22 induces FAK addiction in esophageal squamous cell carcinoma (ESCC)."xsd:string |
| http://purl.uniprot.org/citations/35962191 | http://purl.uniprot.org/core/volume | "19"xsd:string |
| http://purl.uniprot.org/citations/35962191 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/35962191 |
| http://purl.uniprot.org/citations/35962191 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/35962191 |
| http://purl.uniprot.org/uniprot/#_A0A059VC25-mappedCitation-35962191 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35962191 |
| http://purl.uniprot.org/uniprot/#_B4DH13-mappedCitation-35962191 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35962191 |
| http://purl.uniprot.org/uniprot/#_B4DWJ1-mappedCitation-35962191 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35962191 |
| http://purl.uniprot.org/uniprot/#_P23743-mappedCitation-35962191 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35962191 |
| http://purl.uniprot.org/uniprot/#_I6L996-mappedCitation-35962191 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35962191 |
| http://purl.uniprot.org/uniprot/#_O00626-mappedCitation-35962191 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35962191 |
| http://purl.uniprot.org/uniprot/#_Q05397-mappedCitation-35962191 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/35962191 |