ArticleCancer discovery2023
Splicing Factor SRSF1 Promotes Pancreatitis and KRASG12D-Mediated Pancreatic Cancer.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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.
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.
Who cites it
52 citing papers in PubMed, 63 citations in OpenAlex.
- MYC-Mediated USP39 Upregulation Stabilizes SRSF1 in Pancreatic Cancer.Molecular cancer research : MCR · 2026Article
- Identifying a better-prognosis pancreatic cancer from its benign inflammatory mimic: a machine learning approach with contrast-enhanced ultrasound for early intervention.Abdominal radiology (New York) · 2026Article
- Review
- SRPK3 exacerbates cardiac ischemia/reperfusion injury by regulating KLF3-mTOR/P70 S6K-mediated autophagy.Acta pharmacologica Sinica · 2026Article
- Transcriptomic regulation of pancreatic acinar cell homeostasis and plasticity.Biochemical Society transactions · 2026Review
- PERK orchestrates an endoplasmic reticulum stress alternative splicing program via CLK1/SRSF1.Nature communications · 2026Article
- Intermolecular 3'UTR-3'UTR interactions drive Wnt gene activation through heteromeric protein assembly.bioRxiv : the preprint server for biology · 2026Article
- CD33 Isoform Splicing Dysregulation: A Molecular Determinant of Microglial Dysfunction in Alzheimer's Disease Pathology.Molecular neurobiology · 2026Review
- [Expression, Prognostic and Functional Analysis of SRSF Family Proteins in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Article
- Splice-switching ASOs targeting the AURKA 5' UTR collapse an SRSF1-AURKA-MYC oncogenic circuit in pancreatic cancer.Molecular cell · 2026Article
- ACSL4-Mediated Ferroptosis and its Biological Functions and Potential Therapeutic Significance in Liver Diseases.Current pharmaceutical design · 2026Review
- The Function of Poly (U) Binding Splicing Factor 60 (PUF60) in Disease Regulation.Anti-cancer agents in medicinal chemistry · 2026Review
- Downregulation of Chromosome 19 miRNA Cluster and the Tumor-Suppressive Role of miR-517a-3p in Choriocarcinoma.Cancer science · 2025Article
- Article
- Long non-coding RNA AFAP1-AS1 promotes alternative splicing of AXIN2 by facilitating SRSFs phase separation to induce drug resistance in lung adenocarcinoma.Molecular cancer · 2025Article
- CK1α in Sertoli cells is essential for testicular development and spermatogenesis in mice.Zoological research · 2025Article
- Spliceosomal GTPase EFTUD2 mediates DDX41 intron retention to promote the malignant progression of ovarian cancer.British journal of cancer · 2025Article
- SPAT inhibits LUAD metastasis by targeting SF1-mediated splicing.Cell death & disease · 2025Article
- FGFR2 Abrogation Intercepts Pancreatic Ductal Adenocarcinoma Development.Cancer research · 2025Article
- SRSF1-mediated alternative splicing regulates bladder cancer progression and cisplatin sensitivity through HIF1A/BNIP3/mitophagy axis.Journal of translational medicine · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Inflammation is strongly associated with pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy. Dysregulated RNA splicing factors have been widely reported in tumorigenesis, but their involvement in pancreatitis and PDAC is not well understood. Here, we report that the splicing factor SRSF1 is highly expressed in pancreatitis, PDAC precursor lesions, and tumors. Increased SRSF1 is sufficient to induce pancreatitis and accelerate KRASG12D-mediated PDAC. Mechanistically, SRSF1 activates MAPK signaling-partly by upregulating interleukin 1 receptor type 1 (IL1R1) through alternative-splicing-regulated mRNA stability. Additionally, SRSF1 protein is destabilized through a negative feedback mechanism in phenotypically normal epithelial cells expressing KRASG12D in mouse pancreas and in pancreas organoids acutely expressing KRASG12D, buffering MAPK signaling and maintaining pancreas cell homeostasis. This negative feedback regulation of SRSF1 is overcome by hyperactive MYC, facilitating PDAC tumorigenesis. Our findings implicate SRSF1 in the etiology of pancreatitis and PDAC, and point to SRSF1-misregulated alternative splicing as a potential therapeutic target. SIGNIFICANCE: We describe the regulation of splicing factor SRSF1 expression in the context of pancreas cell identity, plasticity, and inflammation. SRSF1 protein downregulation is involved in a negative feedback cellular response to KRASG12D expression, contributing to pancreas cell homeostasis. Conversely, upregulated SRSF1 promotes pancreatitis and accelerates KRASG12D-mediated tumorigenesis through enhanced IL1 and MAPK signaling. This article is highlighted in the In This Issue feature, p. 1501.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.