ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR287/097/SRR28794197/SRR28794197_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR287/096/SRR28794196/SRR28794196_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR287/044/SRR28794144/SRR28794144_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR287/043/SRR28794143/SRR28794143_1.fastq.gzprimary200OKGenomicsCold Spring Harbor Laboratoryhttps://www.ebi.ac.uk/ena/browser/view/PRJNA1101971T cells exclusion precludes checkpoint inhibition efficacy in pancreatic ductal adenocarcinoma (PDA) and is mediated by the interaction between T cell CXCR4, and its ligand CXCL12, which is complexed to keratin-19 (KRT19) on the surface of PDA cells. KRT19 secretion is essential to this proccess but is unusual because KRT19 lacks an endoplasmic reticulum (ER)-directing signal peptide (SP). By using ER-restricted TurboID systems and a split-GFP assay, we demonstrate that KRT19 enters the ER via its head domain. In vivo, tumors formed with ER-TurboID cells contain biotinylated KRT19. Additionally, KRT19 is shown to interact with the signal recognition particle and its secretion is sensitive to canonical protein secretion inhibitors. Although keratin-8 (KRT8) co-localizes with KRT19 on the surface of PDA cells, KRT8 does not enter the ER. However, both keratins are externalized via secretory autophagy. Thus, despite lacking a classical SP, PDA cells secrete KRT19 to protect against immune attack.ENAbiochemical pathways, Carcinoma, Peptides, Signal Peptides, Signal Sequences, exocrine gland fluid, degradation, Keratin 19, exocrine gland fluid or secretion, Leader Sequence, external secretion, Neoplasms, Peptide Signal Sequence, Sorting Signals, malignant neoplasm of body of pancreas, pancreatic neoplasm, familial, Pancreas Cancer, pancreas, Signals, Pancreas Cancers, Peptide, Signal Sequence, Peptide Signal Sequences, signal, Pancreas Neoplasm, Peptide Leader Sequence, Pancreatic Neoplasm, Sequences, exocrine gland fluid/secretion, Bodily Secretion, Ca tail of pancreas, Ca head of pancreas, Sequence, Pancreatic Cancer, Leader Signal Peptide, Protein, Signal Peptide, Neoplasm, Protein Sorting, K19, secretion, Pancreatic Acinar, Cell., pancreatic carcinoma, Cytokeratin-19, Keratin-19, Pancreatic, Leader Sequences, Cancer of the Pancreas, Pancreatic Carcinomas, Carcinomas, malignant neoplasm of tail of pancreas, Leader, pancreatic tumor, Peptide Leader, Cancer of Pancreas, biodegradation, catabolism, Pancreatic Carcinoma, malignant neoplasm of head of pancreas, Leader Peptide, Acinar Carcinoma, Peptide Leader Sequences, Signal, Bodily, Cancers, Pancreatic Cancers, Leader Signal Peptides, Pancreas, Pancreatic Acinar Carcinoma, secreted substance, Leader Signal, Secretion, Leader Peptides, bodily secretion, Ca body of pancreas, Cytokeratin 19, Secretions, Sorting Signal, Protein Sorting Signal, biotransformation, PNCA, Peptide Signal, exocrine gland secretion, Pancreas Neoplasms, Pancreatic Acinar Carcinomas, Acinar Carcinomas, pancreatic tumour, pancreas neoplasm, CK-19, CancerfalseSignal peptide-independent secretion of keratin-19 by pancreatic cancer cells2024-05-112024-05-11PRJNA1101971