ArticleCell reports2021
Targeting p130Cas- and microtubule-dependent MYC regulation sensitizes pancreatic cancer to ERK MAPK inhibition.
Erratum issuedOpen access · goldAbstract read
In one paragraph
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 12% of its field
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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Organoids in translation: a bench-to-bedside framework for pancreatic cancer precision medicine.Journal of translational medicine · 2026Pooled it
- βIII-tubulin can act as a brake on extrinsic apoptosis in pancreatic cancer.Cell death & disease · 2026Article
- Characterization and therapeutic suppression of KEAP1-NRF2-driven resistance to KRAS inhibitors in pancreatic and lung cancer.bioRxiv : the preprint server for biology · 2026Article
- IFDlong: a model-based isoform and fusion detector for accurate annotation and quantification of long-read RNA-seq data.Genome biology · 2026Article
- Tumor cell-intrinsic PD-1 in malignant ascites drives ovarian cancer progression via MAPK/ERK signaling.Oncogene · 2026Article
- CRISPR-Cas9 Screening Identifies Resistance Mechanisms to KRAS Inhibition in Pancreatic Cancer.Cancer research · 2026Article
- Article
- Combination of the MTA-Cooperative PRMT5 Inhibitor BMS-986504 and KRAS Inhibitors Is an Effective Treatment Strategy for MTAP-Deleted KRAS-Mutant Pancreatic Cancer.Cancer research · 2025Article
- GEPIA3: Enhanced drug sensitivity and interaction network analysis for cancer research.Nucleic acids research · 2025Article
- Sensitivity to an inhibitor of translation elongation in solid and hematologic cancers.Scientific reports · 2025Article
- A Pan-RAS Inhibitor with a Unique Mechanism of Action Blocks Tumor Growth and Induces Antitumor Immunity in Gastrointestinal Cancer.Cancer research · 2025Article
- "Undruggable KRAS": druggable after all.Genes & development · 2025Review
- Transforming cancer treatment: integrating patient-derived organoids and CRISPR screening for precision medicine.Frontiers in pharmacology · 2025Review
- Emerging AXL Inhibitors in Oncology: Chemical and Biological Advances in Targeted Cancer Therapy.Anti-cancer agents in medicinal chemistry · 2025Review
- Article
- Determining the ERK-regulated phosphoproteome driving KRAS-mutant cancer.Science (New York, N.Y.) · 2024Article
- Mediator kinase inhibition impedes transcriptional plasticity and prevents resistance to ERK/MAPK-targeted therapy in KRAS-mutant cancers.NPJ precision oncology · 2024Article
- Curcumin inhibits the invasion and migration of pancreatic cancer cells by upregulating TFPI-2 to regulate ERK- and JNK-mediated epithelial-mesenchymal transition.European journal of nutrition · 2024Article
- Regulome-wide association study identifies genetically driven accessible regions associated with pancreatic cancer risk.International journal of cancer · 2024Article
- CRISPRingCancers · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
37 authors at 7 institutions in 3 countries.
Andrew M WatersLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Tala O KhatibLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Bjoern PapkeLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Craig M GoodwinLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
G Aaron HobbsLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
J Nathaniel DiehlCurriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Runying YangLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
A Cole EdwardsLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Katherine H WalshBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Rita SulahianBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
James M McFarlandBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Kevin S KapnerBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Thomas S K GilbertDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; UNC Michael Hooker Proteomics Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Clint A StalneckerLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Sehrish JavaidOral and Craniofacial Biomedicine PhD Program, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Anna BarkovskayaInstitute for Cancer Research, Oslo University Hospital, Oslo 0379, Norway.
Kajal R GroverDepartment of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Priya S HibshmanLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Devon R BlakeDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Antje SchaeferLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Katherine M NowakDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Jennifer E KlompLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Tikvah K HayesCurriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Michelle KassnerCancer and Cell Biology Division, Translational Genomic Research Institute, Phoenix, AZ 85004, USA.
Nanyun TangCancer and Cell Biology Division, Translational Genomic Research Institute, Phoenix, AZ 85004, USA.
Olga TanaseichukGenomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.
Kaisheng ChenGenomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.
Yingyao ZhouGenomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.
Manpreet KalkatDepartment of Medical Biophysics, University of Toronto, Toronto, ON M5S, Canada.
Laura E HerringUNC Michael Hooker Proteomics Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Lee M GravesLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Linda Z PennDepartment of Medical Biophysics, University of Toronto, Toronto, ON M5S, Canada.
Hongwei H YinCancer and Cell Biology Division, Translational Genomic Research Institute, Phoenix, AZ 85004, USA.
Andrew J AguirreBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02215, USA; Brigham and Women's Hospital, Boston, MA 02215, USA.
William C HahnBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02215, USA; Brigham and Women's Hospital, Boston, MA 02215, USA.
Adrienne D CoxLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Oral and Craniofacial Biomedicine PhD Program, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Channing J DerLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Oral and Craniofacial Biomedicine PhD Program, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: cjder@med.unc.edu.
University of North Carolina at Chapel Hill · USBroad Institute · USGenomics Institute of the Novartis Research Foundation · USTranslational Genomics Research Institute · USBrigham and Women's Hospital · USUniversity of Toronto · CAOslo University Hospital · NO
Funding
Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5MTissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI SHIVDASANI, RAMESH A · 2007 to 2023
$33.2MIntegrated Training in Cancer Model SystemsT32CA009156 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DER, CHANNING J. · 1985 to 2020
$19.7MThe role of SMAD1 and SATB2 in colon patterningP20GM130457 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI Evan R Delgado · 2020 to 2026
$18.7MWashington University SPORE in Pancreatic CancerP50CA196510 · NCI · WASHINGTON UNIVERSITY · PI HAWKINS, WILLIAM G · 2016 to 2020
$10.9MProject 4: The role of codon bias in RAS tumorigenesisP01CA203657 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DER, CHANNING J. · 2016 to 2020
$7.9MThe Dana-Farber Cancer Institute Cancer Target Discovery and Development CenterU01CA176058 · NCI · DANA-FARBER CANCER INST · PI HAHN, WILLIAM C. · 2013 to 2021
$7.8MTargeting undruggable RAS for cancer treatmentR35CA232113 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DER, CHANNING J. · 2018 to 2024
$6.3MBIOLOGICAL ACTIVITY OF RAS ONCOGENESR01CA042978 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DER, CHANNING J. · 1986 to 2017
$5.9MCANCER CELL BIOLOGY TRAINING PROGRAMT32CA071341 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CHANNING J. DER, Yuliya Pylayeva-Gupta · 1996 to 2026
$5.0MThe Role of RHOA in Diffuse Gastric CancerR01CA224428 · NCI · DANA-FARBER CANCER INST · PI DER, CHANNING J., WANG, TIMOTHY CRAGIN · 2018 to 2022
$3.6MSystematic interrogation of the pancreatic cancer microenvironment in patient-derived specimensU01CA224146 · NCI · DANA-FARBER CANCER INST · PI HAHN, WILLIAM C. · 2017 to 2021
$3.0MNCI NIH HHS F30 CA243253NCI NIH HHS F31 CA216965NCI NIH HHS F32 CA200313NCI NIH HHS F32 CA221005NCI NIH HHS F32 CA232529NCI NIH HHS F32 CA239328NCI NIH HHS K08 CA218420NCI NIH HHS P01 CA203657NCI NIH HHS P30 CA016086NCI NIH HHS P50 CA127003NCI NIH HHS P50 CA196510NCI NIH HHS R01 CA042978NCI NIH HHS R01 CA175747NCI NIH HHS R01 CA224428NCI NIH HHS R21 CA179193NCI NIH HHS R35 CA232113NCI NIH HHS T32 CA009156NCI NIH HHS T32 CA071341NCI NIH HHS U01 CA176058NCI NIH HHS U01 CA199235NCI NIH HHS U01 CA224146NIGMS NIH HHS P20 GM130457NIGMS NIH HHS T32 GM119999
Abstract
To identify therapeutic targets for KRAS mutant pancreatic cancer, we conduct a druggable genome small interfering RNA (siRNA) screen and determine that suppression of BCAR1 sensitizes pancreatic cancer cells to ERK inhibition. Integrative analysis of genome-scale CRISPR-Cas9 screens also identify BCAR1 as a top synthetic lethal interactor with mutant KRAS. BCAR1 encodes the SRC substrate p130Cas. We determine that SRC-inhibitor-mediated suppression of p130Cas phosphorylation impairs MYC transcription through a DOCK1-RAC1-β-catenin-dependent mechanism. Additionally, genetic suppression of TUBB3, encoding the βIII-tubulin subunit of microtubules, or pharmacological inhibition of microtubule function decreases levels of MYC protein in a calpain-dependent manner and potently sensitizes pancreatic cancer cells to ERK inhibition. Accordingly, the combination of a dual SRC/tubulin inhibitor with an ERK inhibitor cooperates to reduce MYC protein and synergistically suppress the growth of KRAS mutant pancreatic cancer. Thus, we demonstrate that mechanistically diverse combinations with ERK inhibition suppress MYC to impair pancreatic cancer proliferation.
Indexed as
AcetamidesApoptosisCalpainCell Line, TumorCell ProliferationCrk-Associated Substrate ProteinDown-RegulationDrug SynergismExtracellular Signal-Regulated MAP KinasesGene Expression Regulation, NeoplasticHalf-LifeHumansMicrotubulesMorpholinesMutationOrganoidsAcetamidesCalpainCrk-Associated Substrate ProteinExtracellular Signal-Regulated MAP KinasesKRAS protein, humanMorpholinesProtein Kinase InhibitorsProto-Oncogene Proteins c-mycProto-Oncogene Proteins p21(ras)Pyridinessrc-Family KinasestirbanibulinTubulinBCAR1calpainERKKRASmicrotubulesMYCp130Caspancreatic cancerTUBB3β-catenin
Identifiers
What OpenQuestion holds
Textmetadata
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.