CDK1 promotes the phosphorylation of KIFC1 to regulate the tumorgenicity of endometrial carcinoma.

Publisher: Asian Society of Gynecologic Oncology Country of Publication: Korea (South) NLM ID: 101483150 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2005-0399 (Electronic) Linking ISSN: 20050380 NLM ISO Abbreviation: J Gynecol Oncol Subsets: MEDLINE

Publication: June 2011-: Seoul : Asian Society of Gynecologic Oncology : Taehan Puin Chongyang Hakhoe
Original Publication: Seoul : Korean Society of Gynecologic Oncology and Colposcopy, June 2008-

Endometrial Neoplasms*/pathology ; Endometrial Neoplasms*/metabolism ; Endometrial Neoplasms*/genetics ; CDC2 Protein Kinase*/metabolism ; CDC2 Protein Kinase*/genetics ; Kinesins*/metabolism ; Kinesins*/genetics ; Mice, Nude* ; Proto-Oncogene Proteins c-akt*/metabolism; Female ; Humans ; Phosphorylation ; Cell Line, Tumor ; Animals ; Mice ; Phosphatidylinositol 3-Kinases/metabolism ; Cell Movement ; Cell Proliferation ; Apoptosis ; Signal Transduction ; Middle Aged

Objective: This study aims to clarify the mechanical action of cyclin-dependent protein kinase 1 (CDK1) in the development of endometrial carcinoma (EMCA), which may be associated with the phosphorylation of kinesin family member C1 (KIFC1) and further activate the PI3K/AKT pathway.
Methods: The protein and gene expression of CDK1 in EMCA tissues and tumor cell lines were evaluated by western blot, quantitative polymerase chain reaction, and immunohistochemistry staining. Next, Cell Counting Kit-8 and colony formation assay detected cell survival and proliferation. Cell migration and invasion were measured by Transwell assay. Cell apoptosis and cell cycle were tested by flow cytometry. Immunofluorescence staining of γH2AX was used to evaluate DNA damage, respectively. Subsequently, a co-immunoprecipitation assay was used to detect the interaction between CDK1 and KIFC1. The phosphorylated protein of KIFC1 and PI3K/AKT was detected by western blot. Finally, the effect of CDK1 on the tumor formation of EMCA was evaluated in a nude mouse xenograft model.
Results: CDK1 was highly expressed in EMCA tumor cell lines and tissues, which contributed to cell survival, proliferation, invasion, and migration, inhibited cell apoptosis, and induced DNA damage of EMCA cells dependent on the phosphorylation of KIFC1. Moreover, the CDK1-KIFC1 axis further activated PI3K/AKT pathway. Finally, CDK1 knockdown repressed tumor formation of EMCA in vivo.
Conclusion: We report that increased CDK1 promotes tumor progression and identified it as a potential prognostic marker and therapeutic target of EMCA.
Competing Interests: No potential conflict of interest relevant to this article was reported.
(© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

BMC Womens Health. 2022 Nov 24;22(1):470. (PMID: 36434592)
J Transl Med. 2022 Feb 5;20(1):78. (PMID: 35123514)
RNA Biol. 2021 Apr;18(4):576-586. (PMID: 32914682)
Adv Exp Med Biol. 2016;899:1-10. (PMID: 27325258)
Med Sci Monit. 2020 Aug 31;26:e925289. (PMID: 32863381)
Nat Commun. 2021 Jan 4;12(1):20. (PMID: 33397932)
Gynecol Oncol. 2016 Oct;143(1):168-178. (PMID: 27473926)
Semin Cancer Biol. 2022 Oct;85:164-184. (PMID: 33905873)
Development. 2022 Mar 1;149(5):. (PMID: 35142352)
J Cell Physiol. 2019 Jul;234(7):11227-11234. (PMID: 30488492)
Oncogene. 2019 Aug;38(33):6123-6141. (PMID: 31285549)
Biomark Med. 2015;9(4):383-90. (PMID: 25808442)
Trends Cell Biol. 2022 Jan;32(1):30-44. (PMID: 34304958)
EMBO J. 2021 Jun 1;40(11):e99692. (PMID: 33856059)
Aging (Albany NY). 2019 Dec 29;11(24):12773-12792. (PMID: 31895691)
Appl Microbiol Biotechnol. 2019 Aug;103(15):6231-6243. (PMID: 31147754)
Cell Death Dis. 2019 May 24;10(6):402. (PMID: 31127080)
Nucleic Acids Res. 2021 Jun 4;49(10):5537-5552. (PMID: 33999206)
Clin Transl Oncol. 2021 Sep;23(9):1743-1751. (PMID: 33721187)
J Cancer. 2021 Feb 22;12(8):2206-2215. (PMID: 33758599)
Cell Death Dis. 2023 Jan 9;14(1):11. (PMID: 36624090)
Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820964217. (PMID: 33034273)
Appl Biochem Biotechnol. 2023 Nov;195(11):6893-6912. (PMID: 36951938)
Theranostics. 2018 Jun 13;8(14):3737-3750. (PMID: 30083256)
Pharmacol Res. 2019 Jan;139:471-488. (PMID: 30508677)
J Pathol. 2021 Apr;253(4):355-365. (PMID: 33368243)
J Thorac Dis. 2016 Oct;8(10):2911-2923. (PMID: 27867568)
Cell Death Dis. 2021 May 22;12(6):529. (PMID: 34023852)
J Transl Med. 2022 Oct 2;20(1):444. (PMID: 36184616)
Lancet. 2022 Apr 9;399(10333):1412-1428. (PMID: 35397864)
Oxid Med Cell Longev. 2021 Mar 25;2021:6634821. (PMID: 33833852)
J Bioenerg Biomembr. 2021 Dec;53(6):703-713. (PMID: 34729671)
EMBO J. 2014 Feb 18;33(4):385-99. (PMID: 24510915)

2022K58 China A Key Science and Technology Project of Zhejiang Province Quzhou City

Keywords: Cyclin-Dependent Protein Kinase 1; Endometrial Carcinoma; KIFC1; PI3K/AKT; Tumor Progression

EC 2.7.11.22 (CDC2 Protein Kinase)
EC 3.6.4.4 (Kinesins)
EC 2.7.11.22 (CDK1 protein, human)
0 (KIFC1 protein, human)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
EC 2.7.1.- (Phosphatidylinositol 3-Kinases)

Date Created: 20240308 Date Completed: 20240909 Latest Revision: 20241030

20250114

PMC11390247

10.3802/jgo.2024.35.e68

38456590