Research progress of Aurora kinase A in colorectal cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHU Xiang ¹ , WANG Weigang ¹ , ZHAO Fukun ¹ , DONG Hexiang ¹ ,  YU Yongjiang ²

1. The First Clinical School of Lanzhou University, Lanzhou 730000, P. R. China;
2. Department of Gastrointestinal and Abdominal Hernia, The First Hospital of Lanzhou University, Lanzhou 730000, P. R. China;

Corresponding author：

YU Yongjiang, Email: ylongy@163.com

Keywords：

Aurora kinase A; colorectal cancer; inhibitor

DOI：

10.7507/1007-9424.202206075

Video：

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Objective To understand the research progress of Aurora kinase A (AURKA) in colorectal cancer, so as to provide new ideas for treatment of colorectal cancer. Method The relevant to literature on AURKA and its relation with colorectal cancer was searched and reviewed. Results The AURKA was a member of the polygenic family of mitosis/threonine protein kinases. The studies in recent years had found that the AURKA not only played an important role in the regulation in the cell cycle processes, but also played a different role outside the cell cycle. The AURKA abnormally expressed in a variety of malignancies, including colorectal cancer, and was associated with a poor prognosis in patients, and many inhibitors against AURKA were developed and evaluated at different stages of clinical study. Conclusion As a key gene in the occurrence and development of colorectal cancer, AURKA should be further studied to clarify its specific mechanism of action, and targeted drugs may be developed.

Citation： ZHU Xiang, WANG Weigang, ZHAO Fukun, DONG Hexiang, YU Yongjiang. Research progress of Aurora kinase A in colorectal cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(12): 1674-1679. doi: 10.7507/1007-9424.202206075 Copy

1.	Siegel RL, Miller KD, Goding Sauer A, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin, 2020, 70(3): 145-164.
2.	Dekker E, Tanis PJ, Vleugels JLA, et al. Colorectal cancer. Lancet, 2019, 394(10207): 1467-1480.
3.	Giovannucci E. Molecular biologic and epidemiologic insights for preventability of colorectal cancer. J Natl Cancer Inst, 2022, 114(5): 645-650.
4.	Cheng X, Wang J, Lu S, et al. Aurora kinase A (AURKA) promotes the progression and imatinib resistance of advanced gastrointestinal stromal tumors. Cancer Cell Int, 2021, 21(1): 407. doi: 10.1186/s12935-021-02111-7.
5.	Jian F, Che X, Zhang J, et al. The long-noncoding RNA SOCS2-AS1 suppresses endometrial cancer progression by regulating AURKA degradation. Cell Death Dis, 2021, 12(4): 351. doi: 10.1038/s41419-021-03595-x.
6.	Long Q, An X, Chen M, et al. PUF60/AURKA axis contributes to tumor progression and malignant phenotypes in bladder cancer. Front Oncol, 2020, 10: 568015. doi: 10.3389/fonc.2020.568015.
7.	Metselaar DS, du Chatinier A, Meel MH, et al. AURKA and PLK1 inhibition selectively and synergistically block cell cycle progression in diffuse midline glioma. iScience, 2022, 25(6): 104398. doi: 10.1016/j.isci.2022.104398.
8.	Moreira-Nunes CA, Mesquita FP, Portilho AJS, et al. Targeting Aurora kinases as a potential prognostic and therapeutical biomarkers in pediatric acute lymphoblastic leukaemia. Sci Rep, 2020, 10(1): 21272. doi: 10.1038/s41598-020-78024-8.
9.	Peng F, Xu J, Cui B, et al. Oncogenic AURKA-enhanced N6-methyladenosine modification increases DROSHA mRNA stability to transactivate STC1 in breast cancer stem-like cells. Cell Res, 2021, 31(3): 345-361.
10.	Shen Z, Yin L, Zhou H, et al. Combined inhibition of AURKA and HSF1 suppresses proliferation and promotes apoptosis in hepatocellular carcinoma by activating endoplasmic reticulum stress. Cell Oncol (Dordr), 2021, 44(5): 1035-1049.
11.	Sooreshjani MA, Kamra M, Zoubeidi A, et al. Reciprocal deregulation of NKX3.1 and AURKA axis in castration-resistant prostate cancer and NEPC models. J Biomed Sci, 2021, 28(1): 68. doi: 10.1186/s12929-021-00765-z.
12.	Sun H, Wang H, Wang X, et al. Aurora-A/SOX8/FOXK1 signaling axis promotes chemoresistance via suppression of cell senescence and induction of glucose metabolism in ovarian cancer organoids and cells. Theranostics, 2020, 10(15): 6928-6945.
13.	Wang J, Hu T, Wang Q, et al. Repression of the AURKA-CXCL5 axis induces autophagic cell death and promotes radiosensitivity in non-small-cell lung cancer. Cancer Lett, 2021, 509: 89-104.
14.	Xie Y, Zhu S, Zhong M, et al. Inhibition of Aurora kinase A induces necroptosis in pancreatic carcinoma. Gastroenterology, 2017, 153(5): 1429-1443.
15.	Du R, Huang C, Liu K, et al. Targeting AURKA in cancer: molecular mechanisms and opportunities for cancer therapy. Mol Cancer, 2021, 20(1): 15. doi: 10.1186/s12943-020-01305-3.
16.	Dutertre S, Descamps S, Prigent C. On the role of Aurora-A in centrosome function. Oncogene, 2002, 21(40): 6175-6183.
17.	Tanner MM, Tirkkonen M, Kallioniemi A, et al. Increased copy number at 20q13 in breast cancer: defining the critical region and exclusion of candidate genes. Cancer Res, 1994, 54(16): 4257-4260.
18.	Sen S, Zhou H, White RA. A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines. Oncogene, 1997, 14(18): 2195-2200.
19.	Nigg EA. Mitotic kinases as regulators of cell division and its checkpoints. Nat Rev Mol Cell Biol, 2001, 2(1): 21-32.
20.	Carmena M, Wheelock M, Funabiki H, et al. The chromosomal passenger complex (CPC): from easy rider to the godfather of mitosis. Nat Rev Mol Cell Biol, 2012, 13(12): 789-803.
21.	Carmena M, Earnshaw WC. The cellular geography of Aurora kinases. Nat Rev Mol Cell Biol, 2003, 4(11): 842-854.
22.	Korobeynikov V, Deneka AY, Golemis EA. Mechanisms for nonmitotic activation of Aurora-A at cilia. Biochem Soc Trans, 2017, 45(1): 37-49.
23.	Nikonova AS, Astsaturov I, Serebriiskii IG, et al. Aurora A kinase (AURKA) in normal and pathological cell division. Cell Mol Life Sci, 2013, 70(4): 661-687.
24.	Floyd S, Pines J, Lindon C. APC/C Cdh1 targets Aurora kinase to control reorganization of the mitotic spindle at anaphase. Curr Biol, 2008, 18(21): 1649-1658.
25.	Goepfert TM, Brinkley BR. The centrosome-associated Aurora/Ipl-like kinase family. Curr Top Dev Biol, 2000, 49: 331-342.
26.	Willems E, Dedobbeleer M, Digregorio M, et al. The functional diversity of Aurora kinases: a comprehensive review. Cell Div, 2018, 13: 7. doi: 10.1186/s13008-018-0040-6.
27.	Blengini CS, Ibrahimian P, Vaskovicova M, et al. Aurora kinase A is essential for meiosis in mouse oocytes. PLoS Genet, 2021, 17(4): e1009327. doi: 10.1371/journal.pgen.1009327.
28.	Nguyen AL, Drutovic D, Vazquez BN, et al. Genetic interactions between the Aurora kinases reveal new requirements for AURKB and AURKC during oocyte meiosis. Curr Biol, 2018, 28(21): 3458-3468.
29.	Bertolin G, Tramier M. Insights into the non-mitotic functions of Aurora kinase A: more than just cell division. Cell Mol Life Sci, 2020, 77(6): 1031-1047.
30.	Ma HT, Poon RYC. Aurora kinases and DNA damage response. Mutat Res, 2020, 821: 111716. doi: 10.1016/j.mrfmmm.2020.111716.
31.	Bertolin G, Bulteau AL, Alves-Guerra MC, et al. Aurora kinase A localises to mitochondria to control organelle dynamics and energy production. Elife, 2018, 7: e38111. doi: 10.7554/eLife.38111.
32.	Lee DF, Su J, Ang YS, et al. Regulation of embryonic and induced pluripotency by Aurora kinase-p53 signaling. Cell Stem Cell, 2012, 11(2): 179-194.
33.	Cammareri P, Scopelliti A, Todaro M, et al. Aurora-A is essential for the tumorigenic capacity and chemoresistance of colorectal cancer stem cells. Cancer Res, 2010, 70(11): 4655-4665.
34.	Bischoff JR, Anderson L, Zhu Y, et al. A homologue of Drosophila Aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J, 1998, 17(11): 3052-3065.
35.	Gerlach U, Kayser G, Walch A, et al. Centrosome-, chromosomal-passenger- and cell-cycle-associated mRNAs are differentially regulated in the development of sporadic colorectal cancer. J Pathol, 2006, 208(4): 462-472.
36.	Miralaei N, Majd A, Ghaedi K, et al. Integrated pan-cancer of AURKA expression and drug sensitivity analysis reveals increased expression of AURKA is responsible for drug resistance. Cancer Med, 2021, 10(18): 6428-6441.
37.	Lam AK, Ong K, Ho YH. Aurora kinase expression in colorectal adenocarcinoma: correlations with clinicopathological features, p16 expression, and telomerase activity. Hum Pathol, 2008, 39(4): 599-604.
38.	Wang-Bishop L, Chen Z, Gomaa A, et al. Inhibition of AURKA reduces proliferation and survival of gastrointestinal cancer cells with activated KRAS by preventing activation of RPS6KB1. Gastroenterology, 2019, 156(3): 662-675.
39.	Lassmann S, Weis R, Makowiec F, et al. Array CGH identifies distinct DNA copy number profiles of oncogenes and tumor suppressor genes in chromosomal- and microsatellite-unstable sporadic colorectal carcinomas. J Mol Med (Berl), 2007, 85(3): 293-304.
40.	Lassmann S, Danciu M, Müller M, et al. Aurora A is differentially expressed and regulated in chromosomal and microsatellite instable sporadic colorectal cancers. Mod Pathol, 2009, 22(10): 1385-1397.
41.	Goos JA, Coupe VM, Diosdado B, et al. Aurora kinase A (AURKA) expression in colorectal cancer liver metastasis is associated with poor prognosis. Br J Cancer, 2013, 109(9): 2445-2452.
42.	Li M, Gao K, Chu L, et al. The role of Aurora-A in cancer stem cells. Int J Biochem Cell Biol, 2018, 98: 89-92.
43.	Liu X, Zhang Y, Wu S, et al. Palmatine induces G2/M phase arrest and mitochondrial-associated pathway apoptosis in colon cancer cells by targeting AURKA. Biochem Pharmacol, 2020, 175: 113933. doi: 10.1016/j.bcp.2020.113933.
44.	Tang J, Yang L, Li Y, et al. ARID3A promotes the development of colorectal cancer by upregulating AURKA. Carcinogenesis, 2021, 42(4): 578-586.
45.	Wu C, Lyu J, Yang EJ, et al. Targeting AURKA-CDC25C axis to induce synthetic lethality in ARID1A-deficient colorectal cancer cells. Nat Commun, 2018, 9(1): 3212. doi: 10.1038/s41467-018-05694-4.
46.	Sillars-Hardebol AH, Carvalho B, Tijssen M, et al. TPX2 and AURKA promote 20q amplicon-driven colorectal adenoma to carcinoma progression. Gut, 2012, 61(11): 1568-1575.
47.	Takahashi Y, Sheridan P, Niida A, et al. The AURKA/TPX2 axis drives colon tumorigenesis cooperatively with MYC. Ann Oncol, 2015, 26(5): 935-942.
48.	Lai CH, Huang YC, Lee JC, et al. Translational upregulation of Aurora-A by hnRNP Q1 contributes to cell proliferation and tumorigenesis in colorectal cancer. Cell Death Dis, 2017, 8(1): e2555. doi: 10.1038/cddis.2016.479.
49.	Shionome Y, Yan L, Liu S, et al. Integrity of p53 associated pathways determines induction of apoptosis of tumor cells resistant to Aurora-A kinase inhibitors. PLoS One, 2013, 8(1): e55457. doi: 10.1371/journal.pone.0055457.
50.	Stefani C, Miricescu D, Stanescu-Spinu II, et al. Growth factors, PI3K/AKT/mTOR and MAPK signaling pathways in colorectal cancer pathogenesis: where are we now?. Int J Mol Sci, 2021, 22(19): 10260. doi: 10.3390/ijms221910260.
51.	Sun C, Qu Z, Liu W, et al. The synergistic anti-colon cancer effect of Aurora A inhibitors and AKT inhibitors through PI3K/AKT pathway. Anticancer Agents Med Chem, 2022 Apr 22. doi: 10.2174/1871520622666220422133537.
52.	Hong OY, Kang SY, Noh EM, et al. Aurora kinase A induces migration and invasion by inducing epithelial-to-mesenchymal transition in colon cancer cells. BMB Rep, 2022, 55(2): 87-91.
53.	Jacobsen A, Bosch LJW, Martens-de Kemp SR, et al. Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer. Sci Rep, 2018, 8(1): 7522. doi: 10.1038/s41598-018-24982-z.
54.	Shen ZT, Chen Y, Huang GC, et al. Aurora-A confers radioresistance in human hepatocellular carcinoma by activating NF-κB signaling pathway. BMC Cancer, 2019, 19(1): 1075. doi: 10.1186/s12885-019-6312-y.
55.	Jing XL, Chen SW. Aurora kinase inhibitors: a patent review (2014–2020). Expert Opin Ther Pat, 2021, 31(7): 625-644.
56.	Pitts TM, Bradshaw-Pierce EL, Bagby SM, et al. Antitumor activity of the Aurora A selective kinase inhibitor, alisertib, against preclinical models of colorectal cancer. Oncotarget, 2016, 7(31): 50290-50301.
57.	Tentler JJ, Bradshaw-Pierce EL, Serkova NJ, et al. Assessment of the in vivo antitumor effects of ENMD-2076, a novel multitargeted kinase inhibitor, against primary and cell line-derived human colorectal cancer xenograft models. Clin Cancer Res, 2010, 16(11): 2989-2998.
58.	Payton M, Bush TL, Chung G, et al. Preclinical evaluation of AMG900, a novel potent and highly selective pan-Aurora kinase inhibitor with activity in taxane-resistant tumor cell lines. Cancer Res, 2010, 70(23): 9846-9854.
59.	Chinn DC, Holland WS, Mack PC. Anticancer activity of the Aurora A kinase inhibitor MK-5108 in non-small-cell lung cancer (NSCLC) in vitro as monotherapy and in combination with chemotherapies. J Cancer Res Clin Oncol, 2014, 140(7): 1137-1149.
60.	Torrente L, Maan G, Oumkaltoum Rezig A, et al. High NRF2 levels correlate with poor prognosis in colorectal cancer patients and with sensitivity to the kinase inhibitor AT9283 in vitro. Biomolecules, 2020, 10(10): 1365. doi: 10.3390/biom10101365.
61.	Chu QS, Bouganim N, Fortier C et al. Aurora kinase A inhibitor, LY3295668 erbumine: a phase 1 monotherapy safety study in patients with locally advanced or metastatic solid tumors. Invest New Drugs, 2021, 39(4): 1001-1010.
62.	Qi B, Zhong L, He J et al. Discovery of inhibitors of Aurora/PLK targets as anticancer agents. J Med Chem, 2019, 62(17): 7697-7707.
63.	Kim WH, Jeong P, Kim SW et al. A novel indirubin derivative that increases somatic cell plasticity and inhibits tumorigenicity. Bioorg Med Chem, 2019, 27(13): 2923-2934.
64.	Granat LM, Kambhampati O, Klosek S, et al. The promises and challenges of patient-derived tumor organoids in drug development and precision oncology. Animal Model Exp Med, 2019, 2(3): 150-161.
65.	Boos SL, Loevenich LP, Vosberg S, et al. Disease modeling on tumor organoids implicates AURKA as a therapeutic target in liver metastatic colorectal cancer. Cell Mol Gastroenterol Hepatol, 2022, 13(2): 517-540.

1. Siegel RL, Miller KD, Goding Sauer A, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin, 2020, 70(3): 145-164.
2. Dekker E, Tanis PJ, Vleugels JLA, et al. Colorectal cancer. Lancet, 2019, 394(10207): 1467-1480.
3. Giovannucci E. Molecular biologic and epidemiologic insights for preventability of colorectal cancer. J Natl Cancer Inst, 2022, 114(5): 645-650.
4. Cheng X, Wang J, Lu S, et al. Aurora kinase A (AURKA) promotes the progression and imatinib resistance of advanced gastrointestinal stromal tumors. Cancer Cell Int, 2021, 21(1): 407. doi: 10.1186/s12935-021-02111-7.
5. Jian F, Che X, Zhang J, et al. The long-noncoding RNA SOCS2-AS1 suppresses endometrial cancer progression by regulating AURKA degradation. Cell Death Dis, 2021, 12(4): 351. doi: 10.1038/s41419-021-03595-x.
6. Long Q, An X, Chen M, et al. PUF60/AURKA axis contributes to tumor progression and malignant phenotypes in bladder cancer. Front Oncol, 2020, 10: 568015. doi: 10.3389/fonc.2020.568015.
7. Metselaar DS, du Chatinier A, Meel MH, et al. AURKA and PLK1 inhibition selectively and synergistically block cell cycle progression in diffuse midline glioma. iScience, 2022, 25(6): 104398. doi: 10.1016/j.isci.2022.104398.
8. Moreira-Nunes CA, Mesquita FP, Portilho AJS, et al. Targeting Aurora kinases as a potential prognostic and therapeutical biomarkers in pediatric acute lymphoblastic leukaemia. Sci Rep, 2020, 10(1): 21272. doi: 10.1038/s41598-020-78024-8.
9. Peng F, Xu J, Cui B, et al. Oncogenic AURKA-enhanced N6-methyladenosine modification increases DROSHA mRNA stability to transactivate STC1 in breast cancer stem-like cells. Cell Res, 2021, 31(3): 345-361.
10. Shen Z, Yin L, Zhou H, et al. Combined inhibition of AURKA and HSF1 suppresses proliferation and promotes apoptosis in hepatocellular carcinoma by activating endoplasmic reticulum stress. Cell Oncol (Dordr), 2021, 44(5): 1035-1049.
11. Sooreshjani MA, Kamra M, Zoubeidi A, et al. Reciprocal deregulation of NKX3.1 and AURKA axis in castration-resistant prostate cancer and NEPC models. J Biomed Sci, 2021, 28(1): 68. doi: 10.1186/s12929-021-00765-z.
12. Sun H, Wang H, Wang X, et al. Aurora-A/SOX8/FOXK1 signaling axis promotes chemoresistance via suppression of cell senescence and induction of glucose metabolism in ovarian cancer organoids and cells. Theranostics, 2020, 10(15): 6928-6945.
13. Wang J, Hu T, Wang Q, et al. Repression of the AURKA-CXCL5 axis induces autophagic cell death and promotes radiosensitivity in non-small-cell lung cancer. Cancer Lett, 2021, 509: 89-104.
14. Xie Y, Zhu S, Zhong M, et al. Inhibition of Aurora kinase A induces necroptosis in pancreatic carcinoma. Gastroenterology, 2017, 153(5): 1429-1443.
15. Du R, Huang C, Liu K, et al. Targeting AURKA in cancer: molecular mechanisms and opportunities for cancer therapy. Mol Cancer, 2021, 20(1): 15. doi: 10.1186/s12943-020-01305-3.
16. Dutertre S, Descamps S, Prigent C. On the role of Aurora-A in centrosome function. Oncogene, 2002, 21(40): 6175-6183.
17. Tanner MM, Tirkkonen M, Kallioniemi A, et al. Increased copy number at 20q13 in breast cancer: defining the critical region and exclusion of candidate genes. Cancer Res, 1994, 54(16): 4257-4260.
18. Sen S, Zhou H, White RA. A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines. Oncogene, 1997, 14(18): 2195-2200.
19. Nigg EA. Mitotic kinases as regulators of cell division and its checkpoints. Nat Rev Mol Cell Biol, 2001, 2(1): 21-32.
20. Carmena M, Wheelock M, Funabiki H, et al. The chromosomal passenger complex (CPC): from easy rider to the godfather of mitosis. Nat Rev Mol Cell Biol, 2012, 13(12): 789-803.
21. Carmena M, Earnshaw WC. The cellular geography of Aurora kinases. Nat Rev Mol Cell Biol, 2003, 4(11): 842-854.
22. Korobeynikov V, Deneka AY, Golemis EA. Mechanisms for nonmitotic activation of Aurora-A at cilia. Biochem Soc Trans, 2017, 45(1): 37-49.
23. Nikonova AS, Astsaturov I, Serebriiskii IG, et al. Aurora A kinase (AURKA) in normal and pathological cell division. Cell Mol Life Sci, 2013, 70(4): 661-687.
24. Floyd S, Pines J, Lindon C. APC/C Cdh1 targets Aurora kinase to control reorganization of the mitotic spindle at anaphase. Curr Biol, 2008, 18(21): 1649-1658.
25. Goepfert TM, Brinkley BR. The centrosome-associated Aurora/Ipl-like kinase family. Curr Top Dev Biol, 2000, 49: 331-342.
26. Willems E, Dedobbeleer M, Digregorio M, et al. The functional diversity of Aurora kinases: a comprehensive review. Cell Div, 2018, 13: 7. doi: 10.1186/s13008-018-0040-6.
27. Blengini CS, Ibrahimian P, Vaskovicova M, et al. Aurora kinase A is essential for meiosis in mouse oocytes. PLoS Genet, 2021, 17(4): e1009327. doi: 10.1371/journal.pgen.1009327.
28. Nguyen AL, Drutovic D, Vazquez BN, et al. Genetic interactions between the Aurora kinases reveal new requirements for AURKB and AURKC during oocyte meiosis. Curr Biol, 2018, 28(21): 3458-3468.
29. Bertolin G, Tramier M. Insights into the non-mitotic functions of Aurora kinase A: more than just cell division. Cell Mol Life Sci, 2020, 77(6): 1031-1047.
30. Ma HT, Poon RYC. Aurora kinases and DNA damage response. Mutat Res, 2020, 821: 111716. doi: 10.1016/j.mrfmmm.2020.111716.
31. Bertolin G, Bulteau AL, Alves-Guerra MC, et al. Aurora kinase A localises to mitochondria to control organelle dynamics and energy production. Elife, 2018, 7: e38111. doi: 10.7554/eLife.38111.
32. Lee DF, Su J, Ang YS, et al. Regulation of embryonic and induced pluripotency by Aurora kinase-p53 signaling. Cell Stem Cell, 2012, 11(2): 179-194.
33. Cammareri P, Scopelliti A, Todaro M, et al. Aurora-A is essential for the tumorigenic capacity and chemoresistance of colorectal cancer stem cells. Cancer Res, 2010, 70(11): 4655-4665.
34. Bischoff JR, Anderson L, Zhu Y, et al. A homologue of Drosophila Aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J, 1998, 17(11): 3052-3065.
35. Gerlach U, Kayser G, Walch A, et al. Centrosome-, chromosomal-passenger- and cell-cycle-associated mRNAs are differentially regulated in the development of sporadic colorectal cancer. J Pathol, 2006, 208(4): 462-472.
36. Miralaei N, Majd A, Ghaedi K, et al. Integrated pan-cancer of AURKA expression and drug sensitivity analysis reveals increased expression of AURKA is responsible for drug resistance. Cancer Med, 2021, 10(18): 6428-6441.
37. Lam AK, Ong K, Ho YH. Aurora kinase expression in colorectal adenocarcinoma: correlations with clinicopathological features, p16 expression, and telomerase activity. Hum Pathol, 2008, 39(4): 599-604.
38. Wang-Bishop L, Chen Z, Gomaa A, et al. Inhibition of AURKA reduces proliferation and survival of gastrointestinal cancer cells with activated KRAS by preventing activation of RPS6KB1. Gastroenterology, 2019, 156(3): 662-675.
39. Lassmann S, Weis R, Makowiec F, et al. Array CGH identifies distinct DNA copy number profiles of oncogenes and tumor suppressor genes in chromosomal- and microsatellite-unstable sporadic colorectal carcinomas. J Mol Med (Berl), 2007, 85(3): 293-304.
40. Lassmann S, Danciu M, Müller M, et al. Aurora A is differentially expressed and regulated in chromosomal and microsatellite instable sporadic colorectal cancers. Mod Pathol, 2009, 22(10): 1385-1397.
41. Goos JA, Coupe VM, Diosdado B, et al. Aurora kinase A (AURKA) expression in colorectal cancer liver metastasis is associated with poor prognosis. Br J Cancer, 2013, 109(9): 2445-2452.
42. Li M, Gao K, Chu L, et al. The role of Aurora-A in cancer stem cells. Int J Biochem Cell Biol, 2018, 98: 89-92.
43. Liu X, Zhang Y, Wu S, et al. Palmatine induces G2/M phase arrest and mitochondrial-associated pathway apoptosis in colon cancer cells by targeting AURKA. Biochem Pharmacol, 2020, 175: 113933. doi: 10.1016/j.bcp.2020.113933.
44. Tang J, Yang L, Li Y, et al. ARID3A promotes the development of colorectal cancer by upregulating AURKA. Carcinogenesis, 2021, 42(4): 578-586.
45. Wu C, Lyu J, Yang EJ, et al. Targeting AURKA-CDC25C axis to induce synthetic lethality in ARID1A-deficient colorectal cancer cells. Nat Commun, 2018, 9(1): 3212. doi: 10.1038/s41467-018-05694-4.
46. Sillars-Hardebol AH, Carvalho B, Tijssen M, et al. TPX2 and AURKA promote 20q amplicon-driven colorectal adenoma to carcinoma progression. Gut, 2012, 61(11): 1568-1575.
47. Takahashi Y, Sheridan P, Niida A, et al. The AURKA/TPX2 axis drives colon tumorigenesis cooperatively with MYC. Ann Oncol, 2015, 26(5): 935-942.
48. Lai CH, Huang YC, Lee JC, et al. Translational upregulation of Aurora-A by hnRNP Q1 contributes to cell proliferation and tumorigenesis in colorectal cancer. Cell Death Dis, 2017, 8(1): e2555. doi: 10.1038/cddis.2016.479.
49. Shionome Y, Yan L, Liu S, et al. Integrity of p53 associated pathways determines induction of apoptosis of tumor cells resistant to Aurora-A kinase inhibitors. PLoS One, 2013, 8(1): e55457. doi: 10.1371/journal.pone.0055457.
50. Stefani C, Miricescu D, Stanescu-Spinu II, et al. Growth factors, PI3K/AKT/mTOR and MAPK signaling pathways in colorectal cancer pathogenesis: where are we now?. Int J Mol Sci, 2021, 22(19): 10260. doi: 10.3390/ijms221910260.
51. Sun C, Qu Z, Liu W, et al. The synergistic anti-colon cancer effect of Aurora A inhibitors and AKT inhibitors through PI3K/AKT pathway. Anticancer Agents Med Chem, 2022 Apr 22. doi: 10.2174/1871520622666220422133537.
52. Hong OY, Kang SY, Noh EM, et al. Aurora kinase A induces migration and invasion by inducing epithelial-to-mesenchymal transition in colon cancer cells. BMB Rep, 2022, 55(2): 87-91.
53. Jacobsen A, Bosch LJW, Martens-de Kemp SR, et al. Aurora kinase A (AURKA) interaction with Wnt and Ras-MAPK signalling pathways in colorectal cancer. Sci Rep, 2018, 8(1): 7522. doi: 10.1038/s41598-018-24982-z.
54. Shen ZT, Chen Y, Huang GC, et al. Aurora-A confers radioresistance in human hepatocellular carcinoma by activating NF-κB signaling pathway. BMC Cancer, 2019, 19(1): 1075. doi: 10.1186/s12885-019-6312-y.
55. Jing XL, Chen SW. Aurora kinase inhibitors: a patent review (2014–2020). Expert Opin Ther Pat, 2021, 31(7): 625-644.
56. Pitts TM, Bradshaw-Pierce EL, Bagby SM, et al. Antitumor activity of the Aurora A selective kinase inhibitor, alisertib, against preclinical models of colorectal cancer. Oncotarget, 2016, 7(31): 50290-50301.
57. Tentler JJ, Bradshaw-Pierce EL, Serkova NJ, et al. Assessment of the in vivo antitumor effects of ENMD-2076, a novel multitargeted kinase inhibitor, against primary and cell line-derived human colorectal cancer xenograft models. Clin Cancer Res, 2010, 16(11): 2989-2998.
58. Payton M, Bush TL, Chung G, et al. Preclinical evaluation of AMG900, a novel potent and highly selective pan-Aurora kinase inhibitor with activity in taxane-resistant tumor cell lines. Cancer Res, 2010, 70(23): 9846-9854.
59. Chinn DC, Holland WS, Mack PC. Anticancer activity of the Aurora A kinase inhibitor MK-5108 in non-small-cell lung cancer (NSCLC) in vitro as monotherapy and in combination with chemotherapies. J Cancer Res Clin Oncol, 2014, 140(7): 1137-1149.
60. Torrente L, Maan G, Oumkaltoum Rezig A, et al. High NRF2 levels correlate with poor prognosis in colorectal cancer patients and with sensitivity to the kinase inhibitor AT9283 in vitro. Biomolecules, 2020, 10(10): 1365. doi: 10.3390/biom10101365.
61. Chu QS, Bouganim N, Fortier C et al. Aurora kinase A inhibitor, LY3295668 erbumine: a phase 1 monotherapy safety study in patients with locally advanced or metastatic solid tumors. Invest New Drugs, 2021, 39(4): 1001-1010.
62. Qi B, Zhong L, He J et al. Discovery of inhibitors of Aurora/PLK targets as anticancer agents. J Med Chem, 2019, 62(17): 7697-7707.
63. Kim WH, Jeong P, Kim SW et al. A novel indirubin derivative that increases somatic cell plasticity and inhibits tumorigenicity. Bioorg Med Chem, 2019, 27(13): 2923-2934.
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Research progress of Aurora kinase A in colorectal cancer

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