Evidence map›Paper›PMID 40591600›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Signal peptide-independent secretion of keratin-19 by pancreatic cancer cells.

Philip Moresco, Jonathan P Kastan, Jung-In Yang, Rishvanth Prabakar, Z Larkin Kelley, Francesca Minicozzi, Dexter W Adams, Paolo Cifani, David A Tuveson, Douglas T Fearon

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Signal peptide-independent secretion of keratin-19 by pancreatic cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Philip Moresco *Cancer Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY 11724.ORCID 0000-0003-4020-959X
Jonathan P Kastan *Cancer Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY 11724.ORCID 0000-0001-6454-825X
Jung-In YangCancer Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY 11724.
Rishvanth PrabakarCancer Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY 11724.
Z Larkin KelleyMeyer Cancer Center, Weill Cornell Medicine, New York, NY 10065.ORCID 0000-0002-5598-3636
Francesca MinicozziCancer Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY 11724.ORCID 0009-0007-7910-3342
Dexter W AdamsGraduate Program in Genetics, Stony Brook University, Stony Brook, NY 11794.
Paolo CifaniCancer Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY 11724.
David A TuvesonCancer Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY 11724.ORCID 0000-0002-8017-2712
Douglas T FearonCancer Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY 11724.ORCID 0000-0003-0612-0495

Funding

Single-Cell Biology Shared ResourceP30CA045508 · NCI · COLD SPRING HARBOR LABORATORY · PI John Edward Moses · 1987 to 2026
$118.9M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM008444 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI FROHMAN, MICHAEL A. · 1992 to 2024
$12.6M
Lustgarten Foundation (Lustgarten) 33600314NCI NIH HHS P30 CA045508NIGMS NIH HHS T32 GM008444
6 · The paper itself

Abstract

The exclusion of T cells causes immune escape of pancreatic ductal adenocarcinoma (PDA). T cell exclusion is mediated by the interaction between CXCR4 on T cells and its ligand, CXCL12, which is complexed to keratin-19 (KRT19) on the surface of PDA cells. KRT19 secretion by PDA cells is essential to this process but is unusual because KRT19 lacks an endoplasmic reticulum (ER)-directing signal peptide (SP). By using biotinylation by an ER-restricted TurboID system and a split-GFP assay in PDA cells, we demonstrate that KRT19 enters the ER via its "head" domain. Additionally, KRT19 is shown to interact with the signal recognition particle and its secretion is sensitive to canonical protein secretion inhibitors. In vivo, mouse tumors formed with ER-TurboID-expressing PDA cells contain biotinylated KRT19. In contrast, keratin-8 (KRT8), which colocalizes with KRT19 on the surface of PDA cells, does not enter the ER. Rather, KRT8 is externalized via secretory autophagy possibly in a complex with KRT19. Thus, despite lacking a classical SP, PDA cells secrete KRT19 to capture CXCL12 and protect against immune attack.

Indexed as

Carcinoma, Pancreatic DuctalKeratin-19Pancreatic NeoplasmsProtein Sorting SignalsAnimalsCell Line, TumorChemokine CXCL12Endoplasmic ReticulumHumansKeratin-8MiceReceptors, CXCR4Chemokine CXCL12CXCL12 protein, humanKeratin-19Keratin-8KRT19 protein, humanKRT8 protein, humanProtein Sorting SignalsReceptors, CXCR4endoplasmic reticulumpancreatic cancertumor immunologyunconventional protein secretion

Identifiers

PMID40591600
PMCPMC12260553

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.