Cancer-related Molecular Pathways

This study investigates how NF-κB co-activation enhances p53 accumulation dynamics, impairing DNA repair and revealing a transcriptionally mediated antagonism between p53 and NF-κB.

The paper identifies lung cancer-specific p53 mutants that bind genomic sites but fail to activate transcription, revealing a novel loss-of-function mechanism in lung cancer.

This study identifies MDM2 stabilization of NICD in response to platinum chemotherapy in NSCLC, showing that targeting MDM2 and NICD improves survival and reduces tumor growth.

The paper shows that Noc1 downregulation in Drosophila causes nucleolar stress, increases p53 levels, and specifically upregulates the truncated p53E isoform, which may modulate apoptosis.

This study shows that p53 prevents genome instability by halting cell division under hypo-osmotic stress through G1 arrest and downstream gene activation.

This study analyzes TP53 splice site mutations in somatic and germline tumors, finding distinct transcriptional effects and clinical outcomes.

This paper develops a mouse model with a TP53 nonsense mutation to study tumor development and finds it leads to frequent multicentric or metastatic tumors.

The paper analyzes how neoantigenic properties of TP53 variants correlate with cancer risk and presentation in Li-Fraumeni syndrome carriers.

The paper identifies genes that activate the mitotic stopwatch by CRISPR/Cas9 screening, showing it synergizes with mild p53 activation to halt cell proliferation.

This study identifies a new role for Wee1 in promoting S-phase entry by inhibiting APC/CCdh1, revealing a mechanism that impacts the efficacy and toxicity of Wee1 inhibitors in cancer treatment.

The paper identifies RNA binding by mutant p53 and shows it contributes to mitochondrial dysfunction through altered miRNA processing.

This paper develops a sequential triple-drug strategy targeting p53 mutant cancers, showing it effectively induces cell death while minimizing toxicity to normal cells.

The paper shows that p53 protein abundance in TP53 mutant cancers can be exploited to selectively kill these cells using proximity-inducing small molecules.

This study shows that p53 activity persists in HPV+ HNSCC tumors with WT TP53, leading to better survival and therapeutic vulnerabilities.

The paper develops a mechanistic model of p53 dynamics regulated by STAT1, showing how different oscillatory patterns predict cell fate outcomes like arrest, senescence, and apoptosis.

The paper uses BioID proximity labeling to show p53 interacts with PML nuclear bodies and SUMOylation proteins in HEK293 cells, linking these interactions to differences in p53 transcriptional activity compared to HCT116 cells.

This study shows mutant p53 promotes cancer cell invasion in 3D environments via mevalonate pathway-dependent Rho/ROCK signaling and ECM reorganization.

This study shows that cell size autonomously regulates the G1/S transition in mammalian epidermal stem cells, independent of extracellular signals.

This paper develops AKT-100, a curcumin analogue that targets mutant p53 and STAT3 in gynecologic cancer cells, showing cytotoxicity and synergy with existing therapies.

This study shows that CDK2L and CDK2S isoforms are functionally redundant in supporting both mitotic and meiotic divisions in mice.

This study shows that E2f activation in Sox9+ bile duct cells drives proliferation and transdifferentiation into hepatocytes, initiating hepatocellular carcinoma.

This study shows p53 suppresses E2F1-driven genes by maintaining KDM5B at promoters, inhibiting p300-mediated transcription in response to cisplatin.

The paper develops a mathematical model to study how DNA damage affects cell cycle progression, finding that polyploidisation is a key response in HepG2 cells.

The paper analyzes TP53 mutation patterns across 27 cancer types using data from 10,967 tumor samples, finding missense mutations are most common and mutation burdens vary by cancer type.

This study shows DRx-098D, a peptide disrupting MDM2 dimerisation, effectively inhibits cancer cell growth in TP53 wild-type and mutant cell lines, outperforming Idasanutlin in TP53 null cells.

This study shows CDK11 is critical for cancer cell survival and identifies 1p36 deletions as a biomarker for CDK11 inhibitor sensitivity, but on-target toxicity limits therapeutic efficacy.

This paper develops cyclin A/B macrocyclic inhibitors that induce apoptosis in cancers with high E2F activity by blocking RxL-mediated interactions, showing efficacy in SCLC models.

This study shows that reducing endogenous Myc levels in p53-deficient mice extends tumor-free survival and that tumors compensate by increasing Myc dosage or expression.

This study identifies a role for nuclear phosphoinositides in regulating MDM2 stability and function through interactions with small heat shock proteins, offering a new therapeutic target in cancer.

This study investigates whether consensus DNA sequences can regulate p53 aggregation in wild-type and mutant forms, finding that while consensus DNA inhibits wild-type p53 aggregation, oncogenic mutants evade this regulation and may even enhance aggregation.