{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Almozyan S"],"funding":["King Faisal Specialist Hospital and Research Centre","King Abdulaziz City for Science and Technology"],"pagination":["1402-1412"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5575465"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["141(7)"],"pubmed_abstract":["The expression of PD-L1 in breast cancer is associated with estrogen receptor negativity, chemoresistance and epithelial-to-mesenchymal transition (EMT), all of which are common features of a highly tumorigenic subpopulation of cancer cells termed cancer stem cells (CSCs). Hitherto, the expression and intrinsic role of PD-L1 in the dynamics of breast CSCs has not been investigated. To address this issue, we used transcriptomic datasets, proteomics and several in vitro and in vivo assays. Expression profiling of a large breast cancer dataset (530 patients) showed statistically significant correlation (p < 0.0001, r = 0.36) between PD-L1 expression and stemness score of breast cancer. Specific knockdown of PD-L1 using ShRNA revealed its critical role in the expression of the embryonic stem cell transcriptional factors: OCT-4A, Nanog and the stemness factor, BMI1. Conversely, these factors could be induced upon PD-L1 ectopic expression in cells that are normally PD-L1 negative. Global proteomic analysis hinted for the central role of AKT in the biology of PD-L1 expressing cells. Indeed, PD-L1 positive effect on OCT-4A and Nanog was dependent on AKT activation. Most importantly, downregulation of PD-L1 compromised the self-renewal capability of breast CSCs in vitro and in vivo as shown by tumorsphere formation assay and extreme limiting dilution assay, respectively. This study demonstrates a novel role for PD-L1 in sustaining stemness of breast cancer cells and identifies the subpopulation and its associated molecular pathways that would be targeted upon anti-PD-L1 therapy."],"journal":["International journal of cancer"],"pubmed_title":["PD-L1 promotes OCT4 and Nanog expression in breast cancer stem cells by sustaining PI3K/AKT pathway activation."],"pmcid":["PMC5575465"],"funding_grant_id":["SG‐35–237","RAC# 2140–001"],"pubmed_authors":["Qattan A","Al-Alwan M","Ghebeh H","Almozyan S","Colak D","Al-Harazi O","Mansour F","Al-Mohanna F","Alaiya A"],"additional_accession":[]},"is_claimable":false,"name":"PD-L1 promotes OCT4 and Nanog expression in breast cancer stem cells by sustaining PI3K/AKT pathway activation.","description":"The expression of PD-L1 in breast cancer is associated with estrogen receptor negativity, chemoresistance and epithelial-to-mesenchymal transition (EMT), all of which are common features of a highly tumorigenic subpopulation of cancer cells termed cancer stem cells (CSCs). Hitherto, the expression and intrinsic role of PD-L1 in the dynamics of breast CSCs has not been investigated. To address this issue, we used transcriptomic datasets, proteomics and several in vitro and in vivo assays. Expression profiling of a large breast cancer dataset (530 patients) showed statistically significant correlation (p < 0.0001, r = 0.36) between PD-L1 expression and stemness score of breast cancer. Specific knockdown of PD-L1 using ShRNA revealed its critical role in the expression of the embryonic stem cell transcriptional factors: OCT-4A, Nanog and the stemness factor, BMI1. Conversely, these factors could be induced upon PD-L1 ectopic expression in cells that are normally PD-L1 negative. Global proteomic analysis hinted for the central role of AKT in the biology of PD-L1 expressing cells. Indeed, PD-L1 positive effect on OCT-4A and Nanog was dependent on AKT activation. Most importantly, downregulation of PD-L1 compromised the self-renewal capability of breast CSCs in vitro and in vivo as shown by tumorsphere formation assay and extreme limiting dilution assay, respectively. This study demonstrates a novel role for PD-L1 in sustaining stemness of breast cancer cells and identifies the subpopulation and its associated molecular pathways that would be targeted upon anti-PD-L1 therapy.","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017 Oct","modification":"2025-04-04T03:06:21.579Z","creation":"2019-03-27T02:54:49Z"},"accession":"S-EPMC5575465","cross_references":{"pubmed":["28614911"],"doi":["10.1002/ijc.30834"]}}