Protein kinase, membrane‑associated tyrosine/threonine 1 is associated with the progression of colorectal cancer

Jeong,Dongjun; Kim,Hyeongjoo; Kim,Doyeon; Ban,Seona; Oh,Seunghyun; Ji,Sanghee; Kang,Donghuyn; Lee,Hyunyong; Ahn,Tae Sung; Kim,Han Jo; Bae,Sang Byung; Lee,Moon Soo; Kim,Chang‑Jin; Kwon,Hyog Young; Baek,Moo‑Jun

doi:10.3892/or.2018.6371

Protein kinase, membrane‑associated tyrosine/threonine 1 is associated with the progression of colorectal cancer

Authors:
- Dongjun Jeong
- Hyeongjoo Kim
- Doyeon Kim
- Seona Ban
- Seunghyun Oh
- Sanghee Ji
- Donghuyn Kang
- Hyunyong Lee
- Tae Sung Ahn
- Han Jo Kim
- Sang Byung Bae
- Moon Soo Lee
- Chang‑Jin Kim
- Hyog Young Kwon
- Moo‑Jun Baek
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Affiliations: Department of Pathology, College of Medicine, Soonchunhyang University, Cheonan, Chungcheongnam‑do 31151, Republic of Korea, Soonchunhyang Medical Science Research Institute, College of Medicine, Soonchunhyang University, Cheonan, Chungcheongnam‑do 31151, Republic of Korea, Department of Surgery, College of Medicine, Soonchunhyang University, Cheonan, Chungcheongnam‑do 31151, Republic of Korea, Department of Oncology, College of Medicine, Soonchunhyang University, Cheonan, Chungcheongnam‑do 31151, Republic of Korea, Soonchunhyang Institute of Medi‑bio Science (SIMS), Soonchunhyang University, Cheonan, Chungcheongnam‑do 31151, Republic of Korea
Published online on: April 13, 2018 https://doi.org/10.3892/or.2018.6371
Pages: 2829-2836

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Abstract

The protein kinase, membrane‑associated tyrosine/threonine 1 (PKMYT1) is known to inhibit precocious entry into mitosis by phosphorylating CDK1 at Thr14 and Tyr15 residues. However, the functional importance of PKMYT1 in colorectal cancer (CRC) remains unknown. Thus, it is important to elucidate whether PKYMT1 is indispensable in the tumorigenesis of CRC. To investigate the functional importance of PKMYT1 in CRC tumorigenesis, PKMYT1 was knocked down in CRC cell lines such as SW480, SW620, HCT116 and HT29 by siRNA. PKMYT1‑depleted CRC cells were analyzed to determine proliferation, migration, invasion and colony forming ability. In addition, 179 patient‑derived samples were used to find the correlation of the expression of PKMYT1 with the prognosis of CRC patients. By siRNA‑mediated loss of function of PKMYT1, we observed that proliferation, migration, invasion and colony forming ability of CRC cell lines were significantly impaired in the absence of PKMYT1 in vitro. Furthermore, by analyzing patient‑derived samples, we revealed the association of PKMYT1 with the overall survival rate of CRC patients. These results indicated that PKMYT1 plays an essential oncogenic role in CRC and could serve as a good therapeutic target for the treatment of CRC.

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1	Van Roosbroeck S, Hoeck S and Van Hal G: Population-based screening for colorectal cancer using an immunochemical faecal occult blood test: A comparison of two invitation strategies. Cancer Epidemiol. 36:e317–e324. 2012. View Article : Google Scholar : PubMed/NCBI
2	Elias E, Mukherji D, Faraj W, Khalife M, Dimassi H, Eloubeidi M, Hattoum H, Abou-Alfa GK, Saleh A and Shamseddine A: Lymph-node ratio is an independent prognostic factor in patients with stage III colorectal cancer: A retrospective study from the Middle East. World J Surg Oncol. 10:632012. View Article : Google Scholar : PubMed/NCBI
3	Deschoolmeester V, Baay M, Specenier P, Lardon F and Vermorken JB: A review of the most promising biomarkers in colorectal cancer: One step closer to targeted therapy. Oncologist. 15:699–731. 2010. View Article : Google Scholar : PubMed/NCBI
4	Jung KW, Won YJ, Kong HJ, Oh CM, Seo HG and Lee JS: Cancer statistics in Korea: Incidence, mortality, survival and prevalence in 2010. Cancer Res Treat. 45:1–14. 2013. View Article : Google Scholar : PubMed/NCBI
5	Jemal A, Siegel R, Xu J and Ward E: Cancer statistics, 2010. CA Cancer J Clin. 60:277–300. 2010. View Article : Google Scholar : PubMed/NCBI
6	Michor F, Iwasa Y, Lengauer C and Nowak MA: Dynamics of colorectal cancer. Semin Cancer Biol. 15:484–493. 2005. View Article : Google Scholar : PubMed/NCBI
7	Satram-Hoang S, Lee L, Yu S, Guduru SR, Gunuganti AR, Reyes C and McKenna E: Comparative effectiveness of chemotherapy in elderly patients with metastatic colorectal cancer. J Gastrointest Cancer. 44:79–88. 2013. View Article : Google Scholar : PubMed/NCBI
8	Tol J and Punt CJ: Monoclonal antibodies in the treatment of metastatic colorectal cancer: A review. Clin Ther. 32:437–453. 2010. View Article : Google Scholar : PubMed/NCBI
9	Wang L, Chen X, Li W and Sheng Z: Antiepidermal growth factor receptor monoclonal antibody improves survival outcomes in the treatment of patients with metastatic colorectal cancer. Anticancer Drugs. 23:155–160. 2012. View Article : Google Scholar : PubMed/NCBI
10	Wilke HJ and Van Cutsem E: Current treatments and future perspectives in colorectal and gastric cancer. Ann Oncol. 14 Suppl 2:ii49–ii55. 2003. View Article : Google Scholar : PubMed/NCBI
11	Chan KM, Wu TH, Cheng CH, Lee WC, Chiang JM, Chen JS and Wang JY: Prognostic significance of the number of tumors and aggressive surgical approach in colorectal cancer hepatic metastasis. World J Surg Oncol. 12:1552014. View Article : Google Scholar : PubMed/NCBI
12	Swiderska M, Choromanska B, Dabrowska E, Konarzewska-Duchnowska E, Choromańska K, Szczurko G, Myśliwiec P, Dadan J, Ladny JR and Zwierz K: The diagnostics of colorectal cancer. Contemp Oncol. 18:1–6. 2014.
13	Feigelson HS, Zeng C, Pawloski PA, Onitilo AA, Richards CS, Johnson MA, Kauffman TL, Webster J, Nyirenda C, Alexander GL, et al: Does KRAS testing in metastatic colorectal cancer impact overall survival? A comparative effectiveness study in a population-based sample. PLoS One. 9:e949772014. View Article : Google Scholar : PubMed/NCBI
14	Schee K, Lorenz S, Worren MM, Günther CC, Holden M, Hovig E, Fodstad O, Meza-Zepeda LA and Flatmark K: Deep sequencing the MicroRNA transcriptome in colorectal cancer. PLoS One. 8:e661652013. View Article : Google Scholar : PubMed/NCBI
15	Elledge SJ: Cell cycle checkpoints: Preventing an identity crisis. Science. 274:1664–1672. 1996. View Article : Google Scholar : PubMed/NCBI
16	Rhind N and Russell P: Signaling pathways that regulate cell division. Cold Spring Harb Perspect Biol. 4:pii:a0059422012. View Article : Google Scholar
17	Norbury C, Blow J and Nurse P: Regulatory phosphorylation of the p34cdc2 protein kinase in vertebrates. EMBO J. 10:3321–3329. 1991.PubMed/NCBI
18	Mueller PR, Coleman TR, Kumagai A and Dunphy WG: Myt1: A membrane-associated inhibitory kinase that phosphorylates Cdc2 on both threonine-14 and tyrosine-15. Science. 270:86–90. 1995. View Article : Google Scholar : PubMed/NCBI
19	Liu F, Stanton JJ, Wu Z and Piwnica-Worms H: The human Myt1 kinase preferentially phosphorylates Cdc2 on threonine 14 and localizes to the endoplasmic reticulum and Golgi complex. Mol Cell Biol. 17:571–583. 1997. View Article : Google Scholar : PubMed/NCBI
20	Choi HS, Bode AM, Shim JH, Lee SY and Dong Z: c-Jun N-terminal kinase 1 phosphorylates Myt1 to prevent UVA-induced skin cancer. Mol Cell Biol. 29:2168–2180. 2009. View Article : Google Scholar : PubMed/NCBI
21	Chow JP and Poon RY: The CDK1 inhibitory kinase MYT1 in DNA damage checkpoint recovery. Oncogene. 32:4778–4788. 2013. View Article : Google Scholar : PubMed/NCBI
22	Toledo CM, Ding Y, Hoellerbauer P, Davis RJ, Basom R, Girard EJ, Lee E, Corrin P, Hart T, Bolouri H, et al: Genome-wide CRISPR-Cas9 screens reveal loss of redundancy between PKMYT1 and WEE1 in glioblastoma stem-like cells. Cell Rep. 13:2425–2439. 2015. View Article : Google Scholar : PubMed/NCBI
23	Parker LL and Piwnica-Worms H: Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase. Science. 257:1955–1957. 1992. View Article : Google Scholar : PubMed/NCBI
24	Watanabe N, Broome M and Hunter T: Regulation of the human WEE1Hu CDK tyrosine 15-kinase during the cell cycle. EMBO J. 14:1878–1891. 1995.PubMed/NCBI
25	Chambers AF, Groom AC and MacDonald IC: Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2:563–572. 2002. View Article : Google Scholar : PubMed/NCBI
26	Lee JJ and Lotze MT: Molecular basis of metastasis. N Engl J Med. 360:1679–1680. 2009.PubMed/NCBI
27	Frisch SM, Schaller M and Cieply B: Mechanisms that link the oncogenic epithelial-mesenchymal transition to suppression of anoikis. J Cell Sci. 126:21–29. 2013. View Article : Google Scholar : PubMed/NCBI
28	Huang RY, Chung VY and Thiery JP: Targeting pathways contributing to epithelial-mesenchymal transition (EMT) in epithelial ovarian cancer. Curr Drug Targets. 13:1649–1653. 2012. View Article : Google Scholar : PubMed/NCBI
29	Jordan NV, Johnson GL and Abell AN: Tracking the intermediate stages of epithelial-mesenchymal transition in epithelial stem cells and cancer. Cell Cycle. 10:2865–2873. 2011. View Article : Google Scholar : PubMed/NCBI
30	Lee K and Nelson CM: New insights into the regulation of epithelial-mesenchymal transition and tissue fibrosis. Int Rev Cell Mol Biol. 294:171–221. 2012. View Article : Google Scholar : PubMed/NCBI
31	Tam WL and Weinberg RA: The epigenetics of epithelial-mesenchymal plasticity in cancer. Nat Med. 19:1438–1449. 2013. View Article : Google Scholar : PubMed/NCBI
32	Thiery JP and Sleeman JP: Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 7:131–142. 2006. View Article : Google Scholar : PubMed/NCBI
33	Yang J and Weinberg RA: Epithelial-mesenchymal transition: At the crossroads of development and tumor metastasis. Dev Cell. 14:818–829. 2008. View Article : Google Scholar : PubMed/NCBI
34	Lee JM, Dedhar S, Kalluri R and Thompson EW: The epithelial-mesenchymal transition: New insights in signaling, development, and disease. J Cell Biol. 172:973–981. 2006. View Article : Google Scholar : PubMed/NCBI
35	Liu L, Wu J, Wang S, Luo X, Du Y, Huang D, Gu D and Zhang F: PKMYT1 promoted the growth and motility of hepatocellular carcinoma cells by activating beta-catenin/TCF signaling. Exp Cell Res. 358:209–216. 2017. View Article : Google Scholar : PubMed/NCBI