Article in Cancer research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
0numbers the graph read from it
0cells of the map it votes in
3citing 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.
Hiroki Kobayashi *Division of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0000-0002-1717-4870
Yosuke Ochiai *Division of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0000-0003-3069-1175
Junya Arai *Division of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0000-0002-4905-7046
Masahiro Hata *Division of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0000-0002-3836-3515
Feijing Wu *Division of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0000-0001-9198-7960
Masaki Sunagawa *Division of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0000-0002-8334-1964
Tadashi IidaDepartment of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID 0000-0001-5491-6012
Taisuke BabaDivision of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID 0000-0002-0189-7396
Ermanno MalagolaDivision of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0000-0001-9294-3097
Takayuki TanakaDivision of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0000-0002-5789-9833
Zhengyu JiangDivision of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0000-0002-3235-0326
Ruth A WhiteDivision of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York.ORCID 0000-0002-4274-4468
Xiaofei ZhiDivision of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0000-0001-8380-2356
Jin QianDivision of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0000-0002-9684-1685
Quin T WaterburyDivision of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0000-0001-6394-9895
Ruhong TuDivision of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0000-0002-7491-3879
Biyun ZhengDivision of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0000-0001-7680-8661
Yi ZengDivision of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0000-0002-5477-6686
Hualong ZhengDivision of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0000-0002-2749-0113
Puran ZhangDivision of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0000-0002-8757-3535
Shuang LiDivision of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0000-0002-2352-3774
Leah B ZamechekDivision of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0000-0003-2863-2950
Jonathan S LaBellaDivision of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0009-0007-6082-7287
Takahiro SugieDepartment of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID 0009-0009-3682-3723
Atsushi EnomotoDepartment of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan.ORCID 0000-0002-9206-6116
Holger K EltzschigDepartment of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas.ORCID 0000-0002-5676-6473
Carmine F PalermoDivision of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0009-0004-6790-5493
Iok In Christine ChioDepartment of Genetics & Development and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, New York.ORCID 0000-0002-3635-2679
Kenneth P OliveDivision of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0000-0002-3392-8994
Timothy C WangDivision of Digestive and Liver Diseases and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.ORCID 0000-0001-5730-3019
Funding
Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3M
The Role of Stem Cells and the Microenvironment in Gastrointestinal CancersR35CA210088 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Timothy Cragin Wang · 2017 to 2026
$10.2M
The Organoid and Cell Culture CoreP30DK132710 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Robert F. Schwabe · 2022 to 2026
$7.2M
THE FUNCTION AND REGULATION OF HISTIDINE DECARBOXYLASE IN GUT INFLAMMATIONR01DK048077 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI WANG, TIMOTHY CRAGIN · 1995 to 2020
$5.9M
Functional Role of HIF-PHDs in ARDSR01HL169519 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Holger K. Eltzschig, Xiaoyi Yuan · 2023 to 2026
$2.7M
Circadian Rhythm as a Therapeutic Target for Perioperative CardioprotectionR01HL165748 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Holger K. Eltzschig, JOCHEN DANIEL MUEHLSCHLEGEL · 2023 to 2026
$2.6M
microRNA miR-147 Dampens Alveolar Epithelial Inflammation During ARDSR01HL154720 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI ELTZSCHIG, HOLGER K. · 2021 to 2024
$2.2M
Targeting MicroRNA miR-122 for the Treatment of Perioperative Liver InjuryR01DK122796 · NIDDK · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI ELTZSCHIG, HOLGER K., JU, CYNTHIA · 2020 to 2023
$1.8M
Targeting Hypoxia-Inducible Factors (HIFs) for Heart and Lung DiseaseR35HL177402 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Holger K. Eltzschig · 2025 to 2026
$1.1M
A multi-wavelength lighsheet microscope for volumetric imagingS10OD023587 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI PETERKA, DARCY S · 2017 to 2017
$236k
Cell Science Research Foundation (The Cell Science Research Foundation)DeGregorio Family Foundation (DFF) Michael F. Price Memorial Grant AwardInternational Medical Research FoundationJapan Agency for Medical Research and Development (AMED) 22ck0106779h0001Japan Agency for Medical Research and Development (AMED) 22gm1210009s0104Japan Society for the Promotion of Science (JSPS) Overseas Research FellowshipMochida Memorial Foundation for Medical and Pharmaceutical Research ( )National Cancer Institute (NCI) P30CA013696National Cancer Institute (NCI) R35CA210088National Heart, Lung, and Blood Institute (NHLBI) R01HL154720National Heart, Lung, and Blood Institute (NHLBI) R01HL154720-03S1National Heart, Lung, and Blood Institute (NHLBI) R01HL165748National Heart, Lung, and Blood Institute (NHLBI) R01HL169519National Heart, Lung, and Blood Institute (NHLBI) R35HL177402National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 5P30DK132710National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) R01DK122796National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) R01DK48077NCI NIH HHS P30 CA013696NCI NIH HHS R35 CA210088NHLBI NIH HHS R01 HL154720NHLBI NIH HHS R01 HL165748NHLBI NIH HHS R01 HL169519NHLBI NIH HHS R35 HL177402NIDDK NIH HHS P30 DK132710NIDDK NIH HHS R01 DK048077NIDDK NIH HHS R01 DK122796NIH HHS S10 OD023587NIH Office of the Director (OD) 1S10OD023587-01Takeda Science Foundation (TSF)U.S. Department of Defense (DOD) W81XWH-21-1-0901
6 · The paper itself
Abstract
Nerves can regulate tumorigenesis and cancer progression. However, clarification of the role of axon guidance molecules in tumorigenesis, innervation, and metastasis is required to better understand the tumor-promoting functions of nerves. Using murine KrasG12D-mutant pancreatic organoids, we screened axon guidance molecules and identified netrin-1 upregulation. Netrin-1 was also upregulated in vivo during pancreatic tumorigenesis in humans and mice. Mutant KRAS and β-adrenergic signaling upregulated netrin-1 and its receptor NEO1 in epithelial cells in part through the MAPK pathway. Ex vivo culture of celiac ganglia showed that netrin-1 promoted the axonogenesis of sympathetic neurons through nerve NEO1. In the Pdx1-Cre;LSL-KrasG12D/+ model, knockout (KO) of Ntn1, which encodes netrin-1, decreased sympathetic innervation and the development of pancreatic intraepithelial neoplasia. Treatment of pancreatic tumor organoids with recombinant netrin-1 enhanced cell growth, epithelial-mesenchymal transition (EMT), and cancer stemness with the upregulation of ZEB1 and SOX9 through NEO1-mediated activation of focal adhesion kinase (FAK). In Pdx1-Cre;LSL-KrasG12D/+;LSL-Trp53R172H/+ mice, Ntn1 KO reduced innervation, FAK phosphorylation, and the features of EMT and stemness to extend mouse survival. In a liver metastasis model of pancreatic ductal adenocarcinoma (PDAC), treatment with a netrin-1-neutralizing antibody or tumoral KO of Neo1 reduced ZEB1 and SOX9 and decreased tumor progression. In contrast, netrin-1 overexpression promoted innervation and the progression of PDAC liver metastasis. These data suggest that the netrin-1/NEO1 axis is a key regulator of PDAC progression, directly influencing cancer cell stemness and EMT while indirectly promoting tumor growth through nerves. Inhibiting the netrin-1 pathway could represent a potential therapeutic approach for PDAC. SIGNIFICANCE: Netrin-1 promotes pancreatic tumorigenesis and metastasis directly and indirectly through nerves, highlighting the importance of tumor cell-nerve cross-talk in cancer and the potential of netrin-1 blockade as a treatment strategy.
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.
Netrin-1 Promotes Pancreatic Tumorigenesis and Innervation through NEO1. · full record | OpenQuestion