CIP2A (Cellular Inhibitor Of PP2A)

The carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a constituent of CSE, downregulated RING1 expression through DNA methyltransferase 1 (DNMT1) activation, whereas inhibition of DNMT1 restored RING1 levels. These findings highlight the DNMT1-RING1-CIP2A axis in lung cancer progression due to smoking and suggest potential therapeutic and diagnostic targets.

The therapeutic role of metformin to treat brain tumors remains debated. Our findings show that drug delivery is essential, as in vivo, tumor growth decreases at concentrations below 10 nanomolar. We propose that sustained CNS metformin levels may improve tmCLIC1 inhibition, providing a basis for optimizing interactions with metformin or related compounds to enhance therapeutic efficacy.

The simultaneous functional disruption of both MiDAS and MMEJ pathways upon CIP2A loss provides rationale for the synthetic lethality observed in BRCA1 or 2-deficient cells. These findings position the CIP2A-TOPBP1 axis as a central regulatory hub for mitotic DNA repair, highlighting therapeutic opportunities in tumours characterised by HR deficiency or elevated replication stress.

We demonstrate this mechanism of DDR activation in multiple systems: keratinocytes expressing only E2, in foreskin keratinocytes immortalized by HPV16, in HPV16 positive keratinocytes derived from a cervical lesion, in pre-neoplastic lesions induced by mouse papillomavirus MmuPV1, in head and neck cancer cell lines that retain E2 expression, and in HPV16 positive oropharyngeal patient derived xenografts that retain E2 expression. ATM inhibition preferentially killed cells expressing E2, presenting a novel strategy for treating HPV early preneoplasia and a large subset of HPV+ oropharyngeal cancers retaining E2 expression and episomal genomes.

Substantial medicinal chemistry efforts are underway to develop therapeutics aimed at modulating CIP2A activity. The development of specific inhibitors of CIP2A that selectively target its expression or protein stability could improve our understanding of CIP2A's function in pulmonary diseases.

Furthermore, UCHL1 knockdown significantly downregulated cyclin D1 expression, arresting the cell cycle in the G1 phase and inhibiting cell proliferation. Collectively, our findings reveal that UCHL1 promotes gastric cancer progression, highlighting it as a potential therapeutic target.

A naturally occurring bioactive substance, "celastrol," is extracted from the root of Tripterygium wilfordii Hook F. Its effectiveness can be enhanced with the support of nanotechnology to overcome its limitations in cancer treatment. However, the toxicity, dosage, and safety assessments of celastrol and nanocelastrol in cancer applications must be further investigated.

CIP2A is a significant prognostic biomarker in lung cancer, contributing to tumor progression through modulation of angiogenesis and metabolic pathways. Exploration of its therapeutic potential and underlying mechanisms is warranted.

Gene enrichment pointed towards changes p53 pathway, protein metabolism, transporter activity, DNA replication, and cell cycle. Our data provide a novel insight into the role of CIP2A in OvCa and the potential of drug repurposing for therapeutic interventions.

CIP2A targets CEMIP to activate NF-κB signaling pathway, which in turn aggravates cartilage destruction and inflammation and ultimately accelerates OA development. Our results suggest the potential role of the CIP2A/CEMIP axis as a therapeutic target for OA.

It was manifested that high expression of CIP2A can aggrandize cell proliferation, migration, and EMT process in DLBC, and triggered the Wnt/β-catenin pathway. This finding implied that CIP2A may serve as a hopeful target for treating DLBC.

We found that in gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) cells, CIP2A degradation via ubiquitination enhanced PP2A phosphatase activity, leading to the dephosphorylation of ATR at Ser428 in the cytoplasm...These findings reveal a novel mechanism of resistance to DNA damage-based cancer drugs and introduce a new action mechanism of LB-100, which works through mtATR-tBid complex-mediated apoptotic dormancy triggered by CIP2A degradation-mediated PP2A activation. Disrupting the mtATR-tBid complex may represent a promising strategy to restore or sensitize resistant cancer cells to apoptosis.