ArticleCell2015
Cancer-associated protein kinase C mutations reveal kinase's role as tumor suppressor.
Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 186 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
186 citing papers in PubMed, 332 citations in OpenAlex.
- A chemigenetic endogenous Ras activity biosensor for live-cell pharmacology.Nature chemical biology · 2026Article
- Targeting lncRNA-regulated macrophage polarization: a novel therapeutic strategy for pancreatic ductal adenocarcinoma.Journal of physiology and biochemistry · 2026Review
- PHLPP is neither a Phosphatase nor a Tumor Suppressor.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Protein kinase C theta: evolution, regulation, and function.The Biochemical journal · 2026Review
- Discovery of novel natural compounds as PKCθ inhibitors: structure-based virtual screening and in vitro evaluation.Journal of computer-aided molecular design · 2026Article
- Unraveling the PKC Inhibitor: A Review on Mechanistic Insight of H-7 and its Significance in Tackling Cancer.Cell biochemistry and biophysics · 2026Review
- STK32C activated IL-6/JAK2/STAT3 signaling and promoted tumor angiogenesis.British journal of cancer · 2026Article
- Modelling the Full-Length Inactive PKC-δ Structure to Explore Regulatory Accessibility and Selective Targeting Opportunities.Pharmaceuticals (Basel, Switzerland) · 2025Article
- PMA exerts anti-leukemia effect in PhCancer cell international · 2025Article
- CaThe journal of physical chemistry. B · 2025Article
- Leveraging sequences missing from the human genome to diagnose cancer.Communications medicine · 2025Article
- miR-126-3p Protects Neonatal Rats With Hypoxic-Ischemic Brain Damage Through Targeting LPR6 via PKC/ERK Signaling Pathway.Physiological research · 2025Article
- Selective chemical and genetic inhibition of PKCβII strongly sensitizes colon cancer cells to anoikis.Molecular biology reports · 2025Article
- Sensitive fluorescent biosensor reveals differential subcellular regulation of PKC.Nature chemical biology · 2025Article
- Protein kinase C zeta promotes thyroid Cancer progression and represents a novel therapeutic target: evidence from specific atypical PKC inhibitor 2-acetyl-1,3-cyclopentanedione inhibitor studies.Frontiers in medicine · 2025Article
- The Potential Therapeutic Applications of CRISPR/Cas9 in the Treatment of Gastrointestinal Cancers.Current molecular medicine · 2025Review
- ASCL1 Restrains ERK1/2 to Promote Survival of a Subset of Neuroendocrine Lung Cancers.Molecular cancer therapeutics · 2024Article
- Protein kinase A and local signaling in cancer.The Biochemical journal · 2024Review
- PKCActa pharmaceutica Sinica. B · 2024Article
- Kinase activities in pancreatic ductal adenocarcinoma with prognostic and therapeutic avenues.Molecular oncology · 2024Article
126 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Protein kinase C (PKC) isozymes have remained elusive cancer targets despite the unambiguous tumor promoting function of their potent ligands, phorbol esters, and the prevalence of their mutations. We analyzed 8% of PKC mutations identified in human cancers and found that, surprisingly, most were loss of function and none were activating. Loss-of-function mutations occurred in all PKC subgroups and impeded second-messenger binding, phosphorylation, or catalysis. Correction of a loss-of-function PKCβ mutation by CRISPR-mediated genome editing in a patient-derived colon cancer cell line suppressed anchorage-independent growth and reduced tumor growth in a xenograft model. Hemizygous deletion promoted anchorage-independent growth, revealing that PKCβ is haploinsufficient for tumor suppression. Several mutations were dominant negative, suppressing global PKC signaling output, and bioinformatic analysis suggested that PKC mutations cooperate with co-occurring mutations in cancer drivers. These data establish that PKC isozymes generally function as tumor suppressors, indicating that therapies should focus on restoring, not inhibiting, PKC activity.
Indexed as
Identifiers
What Socratic 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 Socratic graph.