mProX™ Human WEE1 Stable Cell Line

Liu, Kaiping. et al. "E2F8 exerts cancer-promoting effects by transcriptionally activating RRM2 and E2F8 knockdown synergizes with WEE1 inhibition in suppressing lung adenocarcinoma." Biochemical pharmacology, 2023.
Ribonucleotide reductase (RR) is a crucial rate-limiting enzyme that aids in DNA replication and repair by converting nucleotide diphosphates (NDPs) to deoxyribonucleotide diphosphates (dNDPs). The E2F family of transcription factors plays a key role in regulating gene expression and cell cycle control. Through database and clinical sample analysis, it was observed that E2F8 expression was significantly increased in most lung adenocarcinoma (LUAD) tissues and positively correlated with RRM2 expression. Additionally, high E2F8 and RRM2 expression levels were predictive of a lower 5-year survival rate in LUAD patients. Further experiments demonstrated that E2F8 was essential for LUAD cell proliferation, DNA synthesis, and cell cycle progression through a RRM2-dependent mechanism. This was confirmed by reporter gene, ChIP-qPCR, and DNA pulldown-Western blot assays, which showed that E2F8 directly bound to the RRM2 promoter and activated its transcription. Previous studies have shown that inhibition of the WEE1 kinase can suppress RRM2 phosphorylation and degradation. In the current study, it was discovered that combining E2F8 knockdown with MK-1775, a WEE1 inhibitor undergoing clinical trials, synergistically inhibited LUAD cell proliferation and promoted apoptosis both in vitro and in vivo. These findings suggest that E2F8 acts as a proto-oncogenic transcription activator in LUAD by activating RRM2 expression and targeting both the transcription and degradation mechanisms of RRM2 could result in a stronger inhibitory effect for LUAD treatment, in addition to conventional RR enzyme inhibition.
Liu, Kaiping. et al. "E2F8 exerts cancer-promoting effects by transcriptionally activating RRM2 and E2F8 knockdown synergizes with WEE1 inhibition in suppressing lung adenocarcinoma." Biochemical pharmacology, 2023.
Pubmed: 37863324   DOI: 10.1016/j.bcp.2023.115854

Wang, Wenkuan. et al. "Targeting Dna Damage and Repair Machinery via Delivering WEE1 Inhibitor and Platinum (IV) Prodrugs to Stimulate Sting Pathway for Maximizing Chemo-immunotherapy in Bladder Cancer." Advanced materials (Deerfield Beach, Fla.), 2023.
Cisplatin-based chemotherapy and immune checkpoint inhibitors (ICIs) represent the primary therapeutic approaches for advanced bladder cancer. Resistance to cisplatin often arises from enhanced DNA repair mechanisms, while limited response to ICIs is primarily attributed to immunosuppressive microenvironments and low PD-L1 expression. A novel GSH-responsive nanoparticle, NP2, carrying cisplatin prodrug (Pt (IV)) and WEE1 inhibitor (MK1775), has been engineered. NP2 activates in cancer cells in response to GSH, releasing MK1775 to inhibit WEE1 protein activity, consequently augmenting cisplatin-induced DNA damage. NP2 disrupts DNA repair pathways, triggers interferon gene activation, and inhibits tumor growth in vivo. Moreover, NP2 transforms an "immune cold tumor" into an "immune hot tumor," upregulates PD-L1 expression, and enhances the responsiveness to PD-L1 monoclonal antibody (αPD-L1), leading to sustained immune responses in both primary and metastatic tumors.
Wang, Wenkuan. et al. "Targeting Dna Damage and Repair Machinery via Delivering WEE1 Inhibitor and Platinum (IV) Prodrugs to Stimulate Sting Pathway for Maximizing Chemo-immunotherapy in Bladder Cancer." Advanced materials (Deerfield Beach, Fla.), 2023.
Pubmed: 37849029   DOI: 10.1002/adma.202308762