Research Advance on the Relationship between Wee1 and Tumor Genesis and Progression

Ying Yin (Binzhou Medical University, No. 346 Guanhai Road, Laishan District, Yantai, Shandong, 264003, China)
Guohua Yu (Yantai Yuhuangding Hospital, No. 20 Yuhuangding East Road, Zhifu District, Yantai, Shandong, 264000, China)

Article ID: 2851


In the process of biological genetic information transmission, complete and correct genetic information can make cell mitosis proceed normally.In the development of most tumor cells, G2/M cell cycle checkpoint becomes the key checkpoint in the process of mitosis due to the lack of G1/S cell cycle checkpoint, which mainly depends on the abnormal DNA information blocked by Wee1 protein kinase in G2 phase to enter M phase and prolong the time of G2 phase to complete DNA sequencing So that the normal genetic information can be passed on. Wee1 protein kinase expression is significantly increased in most tumor cells,making it a potential target for tumor therapy.


Wee1 protein kinase;Cell cycle;Wee1 kinase inhibitor;Tumor

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[1] Nakanishi, M., et al., Identification and characterization of human Wee1B, a new member of the Wee1 family of Cdk-inhibitory kinases. Genes Cells, 2000. 5(10): p. 839-47.


[3] Taviaux, S.A. and J.G. Demaille, Localization of human cell cycle regulatory genes CDC25C to 5q31 and WEE1 to 11p15.3-11p15.1 by fluorescence in situ hybridization. Genomics, 1993. 15(1): p. 194-6.


[5] Igarashi, M., et al., Wee1(+)-like gene in human cells. Nature, 1991. 353(6339): p. 80-3.


[7] Owens, L., et al., Activation domain-dependent degradation of somatic Wee1 kinase. J Biol Chem,2010. 285(9): p. 6761-9.


[9] Aligue, R., L. Wu and P. Russell, Regulation of Schizosaccharomyces pombe Wee1 tyrosine kinase.J Biol Chem, 1997. 272(20): p. 13320-5.


[11] Ghelli, L.D.R.A., et al., A WEE1 family business:regulation of mitosis, cancer progression, and therapeutic target. J Hematol Oncol, 2020. 13(1): p. 126.


[13] Geenen, J. and J. Schellens, Molecular Pathways:Targeting the Protein Kinase Wee1 in Cancer.Clin Cancer Res, 2017. 23(16): p. 4540-4544.


[15] Manic, G., et al., Trial Watch: Targeting ATMCHK2 and ATR-CHK1 pathways for anticancer therapy. Mol Cell Oncol, 2015. 2(4): p. e1012976.


[17] Sanchez, Y., et al., Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25. Science,1997. 277(5331): p. 1497-501.


[19] Wenzel, E.S. and A. Singh, Cell-cycle Checkpoints and Aneuploidy on the Path to Cancer. In Vivo,2018. 32(1): p. 1-5.


[21] Kim, H.Y., et al., Targeting the WEE1 kinase as a molecular targeted therapy for gastric cancer. Oncotarget, 2016. 7(31): p. 49902-49916.


[23] Zhang, N., et al., Ropivacaine Inhibits the Growth,Migration and Invasion of Gastric Cancer Through Attenuation of WEE1 and PI3K/AKT Signaling via miR-520a-3p. Onco Targets Ther, 2020.13: p.5309-5321.


[25] Magnussen, G.I., et al., High expression of Wee1 is associated with poor disease-free survival in malignant melanoma: potential for targeted therapy. PLoS One, 2012. 7(6): p. e38254.


[27] Kuzu, O.F., et al., Identification of WEE1 as a target to make AKT inhibition more effective in melanoma. Cancer Biol Ther, 2018. 19(1): p. 53-62.


[29] DiSano, J.A., et al., Loss of miR-155 upregulates WEE1 in metastatic melanoma. Melanoma Res,2019. 29(2): p. 216-219.


[31] Bhattacharya, A., et al., Regulation of cell cycle checkpoint kinase WEE1 by miR-195 in malignant melanoma. Oncogene, 2013. 32(26): p. 3175-83.


[33] Egeland, E.V., et al., Expression and clinical significance of Wee1 in colorectal cancer. Tumour Biol,2016. 37(9): p. 12133-12140.


[35] Ge, X.C., et al., Upregulation of WEE1 is a potential prognostic biomarker for patients with colorectal cancer. Oncol Lett, 2017. 13(6): p. 4341-4348.


[37] Yin, Y., et al., Wee1 inhibition can suppress tumor proliferation and sensitize p53 mutant colonic cancer cells to the anticancer effect of irinotecan. Mol Med Rep, 2018. 17(2): p. 3344-3349.


[39] Webster, P.J., et al., Upregulated WEE1 protects endothelial cells of colorectal cancer liver metastases.Oncotarget, 2017. 8(26): p. 42288-42299.


[41] Bado, I., et al., ERbeta decreases the invasiveness of triple-negative breast cancer cells by regulating mutant p53 oncogenic function. Oncotarget, 2016.7(12): p. 13599-611.


[43] Jin, J., et al., Combined Inhibition of ATR and WEE1 as a Novel Therapeutic Strategy in Triple-Negative Breast Cancer. Neoplasia, 2018. 20(5):p. 478-488.


[45] Ghiasi, N., et al., Tumour suppressive effects of WEE1 gene silencing in breast cancer cells. Asian Pac J Cancer Prev, 2014. 14(11): p. 6605-11.


[47] Yoshida, T., et al., The clinical significance of Cyclin B1 and Wee1 expression in non-small-cell lung cancer. Ann Oncol, 2004. 15(2): p. 252-6.

[48] Ku, B.M., et al., Mutational status of TP53 defines the efficacy of Wee1 inhibitor AZD1775 in KRAS-mutant non-small cell lung cancer. Oncotarget, 2017. 8(40): p. 67526-67537.


[50] Hai, J., et al., Synergy of WEE1 and mTOR Inhibition in Mutant KRAS-Driven Lung Cancers.Clin Cancer Res, 2017. 23(22): p. 6993-7005.


[52] Jhuraney, A., et al., PAXIP1 Potentiates the Combination of WEE1 Inhibitor AZD1775 and Platinum Agents in Lung Cancer. Mol Cancer Ther, 2016.15(7): p. 1669-81.


[54] Sen, T., et al., Targeting AXL and mTOR Pathway Overcomes Primary and Acquired Resistance to WEE1 Inhibition in Small-Cell Lung Cancer. Clin Cancer Res, 2017. 23(20): p. 6239-6253.


[56] Wang, X., et al., Chemotherapy-induced differential cell cycle arrest in B-cell lymphomas affects their sensitivity to Wee1 inhibition. Haematologica,2018. 103(3): p. 466-476.


[58] de Jong, M., et al., Identification of relevant drugable targets in diffuse large B-cell lymphoma using a genome-wide unbiased CD20 guilt-by association approach. PLoS One, 2018. 13(2): p.e0193098.


[60] Restelli, V., et al., Inhibition of CHK1 and WEE1 as a new therapeutic approach in diffuse large B cell lymphomas with MYC deregulation. Br J Haematol,2018. 181(1): p. 129-133.


[62] de Jong, M., et al., WEE1 Inhibition Enhances Anti-Apoptotic Dependency as a Result of Premature Mitotic Entry and DNA Damage. Cancers (Basel),2019. 11(11).


[64] Chila, R., et al., Combined inhibition of Chk1 and Wee1 as a new therapeutic strategy for mantle cell lymphoma. Oncotarget, 2015. 6(5): p. 3394-408.


[66] Zhang, M., et al., WEE1 inhibition by MK1775 as a single-agent therapy inhibits ovarian cancer viability. Oncol Lett, 2017. 14(3): p. 3580-3586.


[68] Bi, S., et al., Wee1 Inhibitor AZD1775 Effectively Inhibits the Malignant Phenotypes of Esophageal Squamous Cell Carcinoma In Vitro and In Vivo.Front Pharmacol, 2019. 10: p. 864.

[69] Jin, M.H., et al., Therapeutic Co-targeting of WEE1 and ATM Downregulates PD-L1 Expression in Pancreatic Cancer. Cancer Res Treat, 2020. 52(1): p.149-166.


[71] Ghelli, L.D.R.A., et al., Synergism Through WEE1 and CHK1 Inhibition in Acute Lymphoblastic Leukemia. Cancers (Basel), 2019. 11(11).


[73] Hu, J., et al., WEE1 inhibition induces glutamine addiction in T-cell acute lymphoblastic leukemia.Haematologica, 2020.


[75] Lewis, C.W., et al., Upregulation of Myt1 Promotes Acquired Resistance of Cancer Cells to Wee1 Inhibition. Cancer Res, 2019. 79(23): p. 5971-5985.


[77] Fang, Y., et al., Sequential Therapy with PARP and WEE1 Inhibitors Minimizes Toxicity while Maintaining Efficacy. Cancer Cell, 2019. 35(6): p. 851-867.e7.


[79] Geenen, J. and J. Schellens, Molecular Pathways:Targeting the Protein Kinase Wee1 in Cancer. Clin Cancer Res, 2017. 23(16): p. 4540-4544.


[81] Liang, J., et al., Genome-Wide CRISPR-Cas9 Screen Reveals Selective Vulnerability of ATRX-Mutant Cancers to WEE1 Inhibition. Cancer Res, 2020. 80(3): p. 510-523.



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