{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["14(1)"],"submitter":["Katara GK"],"funding":["National Cancer Institute"],"pubmed_abstract":["Interleukin (IL)-22 is recognized as a tumor-supporting cytokine and is implicated in the proliferation of multiple epithelial cancers. In breast cancer, the current knowledge of IL-22 function is based on cell line models and little is known about how IL-22 affects the tumor initiation, proliferation, invasion, and metastasis in the in vivo system. Here, we investigated the tumor stage-specific function of IL-22 in disease development by evaluating the stage-by-stage progression of breast cancer in an IL-22 knockout spontaneous breast cancer mouse model. We found that among all the stages, IL-22 is specifically upregulated in tumor microenvironment (TME) during the malignant transformation stage of breast tumor progression. The deletion of IL-22 gene leads to the arrest of malignant transition stage, and reduced invasion and tumor burden. Administration of recombinant IL-22 in the TME does not influence in vivo tumor initiation and proliferation but only promotes malignant transformation of cancer cells. Mechanistically, deletion of IL-22 gene causes downregulation of epithelial-to-mesenchymal transition (EMT)-associated transcription factors in breast tumors, suggesting EMT as the mechanism of regulation of malignancy by IL-22. Clinically, in human breast tumor tissues, increased number of IL-22<sup>+</sup> cells in the TME is associated with an aggressive phenotype of breast cancer. For the first time, this study provides an insight into the tumor stage-specific function of IL-22 in breast tumorigenesis."],"journal":["Molecular oncology"],"pagination":["211-224"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6944104"],"repository":["biostudies-literature"],"pubmed_title":["Interleukin-22 promotes development of malignant lesions in a mouse model of spontaneous breast cancer."],"pmcid":["PMC6944104"],"pubmed_authors":["Kulshrestha A","Riehl V","Schneiderman S","Katara GK","Ibrahim S","Beaman KD"],"additional_accession":[]},"is_claimable":false,"name":"Interleukin-22 promotes development of malignant lesions in a mouse model of spontaneous breast cancer.","description":"Interleukin (IL)-22 is recognized as a tumor-supporting cytokine and is implicated in the proliferation of multiple epithelial cancers. In breast cancer, the current knowledge of IL-22 function is based on cell line models and little is known about how IL-22 affects the tumor initiation, proliferation, invasion, and metastasis in the in vivo system. Here, we investigated the tumor stage-specific function of IL-22 in disease development by evaluating the stage-by-stage progression of breast cancer in an IL-22 knockout spontaneous breast cancer mouse model. We found that among all the stages, IL-22 is specifically upregulated in tumor microenvironment (TME) during the malignant transformation stage of breast tumor progression. The deletion of IL-22 gene leads to the arrest of malignant transition stage, and reduced invasion and tumor burden. Administration of recombinant IL-22 in the TME does not influence in vivo tumor initiation and proliferation but only promotes malignant transformation of cancer cells. Mechanistically, deletion of IL-22 gene causes downregulation of epithelial-to-mesenchymal transition (EMT)-associated transcription factors in breast tumors, suggesting EMT as the mechanism of regulation of malignancy by IL-22. Clinically, in human breast tumor tissues, increased number of IL-22<sup>+</sup> cells in the TME is associated with an aggressive phenotype of breast cancer. For the first time, this study provides an insight into the tumor stage-specific function of IL-22 in breast tumorigenesis.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Jan","modification":"2024-11-08T21:54:43.6Z","creation":"2020-05-22T07:06:02Z"},"accession":"S-EPMC6944104","cross_references":{"pubmed":["31725949"],"doi":["10.1002/1878-0261.12598"]}}