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Discover Oncology
Published in: Discover Oncology 1/2024

Open Access 01-12-2024 | Endometrial Cancer | Research

Mechanism of regulation of KIF23 on endometrial cancer cell growth and apoptosis

Authors: Ruiying Zhuang, Haiyan Liu

Published in: Discover Oncology | Issue 1/2024

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Abstract

Objective

The global incidence of endometrial cancer, a malignant tumor in females, is on the rise. It is one of the most common gynecological cancers. Early-stage endometrial cancers can often be treated successfully with uterine extirpation. However, those diagnosed at a later stage have a poor prognosis and encounter treatment challenges. Therefore, additional research is necessary to develop primary prevention strategies for high-risk women and improve survival rates among patients with endometrial cancer. Hence, gene therapy targeting KIF23 shows promise as an advanced strategy for the treatment of endometrial cancer.

Methods

Immunohistochemistry, Western blotting, and PCR were used to examine the expression of KIF23 and its associated pathway factors in endometrial cancer tissue (specifically Ishikawa and SNGM cells, respectively). We investigated the functional roles of KIF23 using CCK-8, colony-forming proliferation assays, Transwell migration assays, and xenotransplantation in mice.

Results

Immunohistochemistry analysis showed variations in the expression levels of KIF23 between endometrial cancer tissue and normal endometrium tissue. KIF23 downregulated BAX and caspase-3 protein expression while upregulating BCL-2 protein expression. Additionally, knocking out KIF23 inhibits endometrial cancer cell proliferation and migration while promoting cell death. Mechanistically, our study provides evidence that KIF23 promotes endometrial cancer cell proliferation by activating the ERK and AKT/PI3K pathways, while simultaneously inhibiting programmed cell death in endometrial cancer.

Conclusion

Our study provides evidence to support the inhibition of endometrial cancer by KIF23 knockdown. This offers valuable insights for future research on potential therapeutic strategies for this type of cancer.

Graphical Abstract

Appendix
Available only for authorised users
Literature
1.
Banz-Jansen C, Helweg LP, Kaltschmidt B. Endometrial cancer stem cells: where do we stand and where should we go? Int J Mol Sci. 2022;23:6.CrossRef
2.
Connor EV, Rose PG. Management strategies for recurrent endometrial cancer. Expert Rev Anticancer Ther. 2018;18(9):873–85.PubMedCrossRef
3.
van den Heerik A, Horeweg N, de Boer SM, et al. Adjuvant therapy for endometrial cancer in the era of molecular classification: radiotherapy, chemoradiation and novel targets for therapy. Int J Gynecol Cancer. 2021;31(4):594–604.PubMedCrossRef
4.
Garzon S, Uccella S, Zorzato PC, et al. Fertility-sparing management for endometrial cancer: review of the literature. Minerva Med. 2021;112(1):55–69.PubMedCrossRef
5.
Takahashi S, Fusaki N, Ohta S, et al. Downregulation of KIF23 suppresses glioma proliferation. J Neurooncol. 2012;106(3):519–29.PubMedCrossRef
6.
Nislow C, Lombillo VA, Kuriyama R, et al. A plus-end-directed motor enzyme that moves antiparallel microtubules in vitro localizes to the interzone of mitotic spindles. Nature. 1992;359(6395):543–7.PubMedCrossRef
7.
Hirokawa N, Noda Y, Tanaka Y, et al. Kinesin superfamily motor proteins and intracellular transport. Nat Rev Mol Cell Biol. 2009;10(10):682–96.PubMedCrossRef
8.
Miki H, Okada Y, Hirokawa N. Analysis of the kinesin superfamily: insights into structure and function. Trends Cell Biol. 2005;15(9):467–76.PubMedCrossRef
9.
Duangtum N, Junking M, Sawasdee N, et al. Human kidney anion exchanger 1 interacts with kinesin family member 3B (KIF3B). Biochem Biophys Res Commun. 2011;413(1):69–74.PubMedCrossRef
10.
Calligaris D, Verdier-Pinard P, Devred F, et al. Microtubule targeting agents: from biophysics to proteomics. Cell Mol Life Sci. 2010;67(7):1089–104.PubMedCrossRef
11.
Kline-Smith SL, Walczak CE. Mitotic spindle assembly and chromosome segregation: refocusing on microtubule dynamics. Mol Cell. 2004;15(3):317–27.PubMedCrossRef
12.
Vasiliev JM, Gelfand IM, Domnina LV, et al. Effect of colcemid on the locomotory behaviour of fibroblasts. J Embryol Exp Morphol. 1970;24(3):625–40.PubMed
13.
Verhey KJ, Kaul N, Soppina V. Kinesin assembly and movement in cells. Annu Rev Biophys. 2011;40:267–88.PubMedCrossRef
14.
Cross RA, McAinsh A. Prime movers: the mechanochemistry of mitotic kinesins. Nat Rev Mol Cell Biol. 2014;15(4):257–71.PubMedCrossRef
15.
16.
Hirokawa N, Noda Y, Okada Y. Kinesin and dynein superfamily proteins in organelle transport and cell division. Curr Opin Cell Biol. 1998;10(1):60–73.PubMedCrossRef
17.
18.
Hirokawa N, Tanaka Y. Kinesin superfamily proteins (KIFs): Various functions and their relevance for important phenomena in life and diseases. Exp Cell Res. 2015;334(1):16–25.PubMedCrossRef
19.
Zou JX, Duan Z, Wang J, et al. Kinesin family deregulation coordinated by bromodomain protein ANCCA and histone methyltransferase MLL for breast cancer cell growth, survival, and tamoxifen resistance. Mol Cancer Res. 2014;12(4):539–49.PubMedPubMedCentralCrossRef
20.
Lai F, Fernald AA, Zhao N, et al. cDNA cloning, expression pattern, genomic structure and chromosomal location of RAB6KIFL, a human kinesin-like gene. Gene. 2000;248(1–2):117–25.PubMedCrossRef
21.
Liu X, Erikson RL. The nuclear localization signal of mitotic kinesin-like protein Mklp-1: effect on Mklp-1 function during cytokinesis. Biochem Biophys Res Commun. 2007;353(4):960–4.PubMedCrossRef
22.
Sablin EP. Kinesins and microtubules: their structures and motor mechanisms. Curr Opin Cell Biol. 2000;12(1):35–41.PubMedCrossRef
23.
Fujiwara T, Bandi M, Nitta M, et al. Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells. Nature. 2005;437(7061):1043–7.PubMedCrossRef
24.
Yu Y, Feng YM. The role of kinesin family proteins in tumorigenesis and progression: potential biomarkers and molecular targets for cancer therapy. Cancer. 2010;116(22):5150–60.PubMedCrossRef
25.
Xie T, Li X, Ye F, et al. High KIF2A expression promotes proliferation, migration and predicts poor prognosis in lung adenocarcinoma. Biochem Biophys Res Commun. 2018;497(1):65–72.PubMedCrossRef
26.
Liu X, Zhou T, Kuriyama R, et al. Molecular interactions of Polo-like-kinase 1 with the mitotic kinesin-like protein CHO1/MKLP-1. J Cell Sci. 2004;117(Pt 15):3233–46.PubMedCrossRef
27.
28.
Liu Y, Chen H, Dong P, et al. KIF23 activated Wnt/beta-catenin signaling pathway through direct interaction with Amer1 in gastric cancer. Aging (Albany NY). 2020;12(9):8372–96.PubMedCrossRef
29.
Murali R, Soslow RA, Weigelt B. Classification of endometrial carcinoma: more than two types. Lancet Oncol. 2014;15(7):e268–78.PubMedCrossRef
30.
Paleari L. New Strategies for Endometrial Cancer Detection and Management. Int J Mol Sci. 2023;24:7.CrossRef
31.
De Felice F, Marchetti C, Tombolini V, et al. Immune check-point in endometrial cancer. Int J Clin Oncol. 2019;24(8):910–6.PubMedCrossRef
32.
33.
Hunn J, Dodson MK, Webb J, et al. Endometrial cancer–current state of the art therapies and unmet clinical needs: the role of surgery and preoperative radiographic assessment. Adv Drug Deliv Rev. 2009;61(10):890–5.PubMedCrossRef
34.
35.
Zanfagnin V, Ferrero A, Biglia N, et al. The role of surgery in recurrent endometrial cancer. Expert Rev Anticancer Ther. 2016;16(7):741–50.PubMedCrossRef
36.
Bie Y, Zhang Z, Wang X. Adjuvant chemo-radiotherapy in the “sandwich” method for high risk endometrial cancer–a review of literature. BMC Womens Health. 2015;15:50.PubMedPubMedCentralCrossRef
37.
McAlpine J, Leon-Castillo A, Bosse T. The rise of a novel classification system for endometrial carcinoma; integration of molecular subclasses. J Pathol. 2018;244(5):538–49.PubMedCrossRef
38.
Boruban MC, Altundag K, Kilic GS, et al. From endometrial hyperplasia to endometrial cancer: insight into the biology and possible medical preventive measures. Eur J Cancer Prev. 2008;17(2):133–8.PubMedCrossRef
39.
Weigelt B, Banerjee S. Molecular targets and targeted therapeutics in endometrial cancer. Curr Opin Oncol. 2012;24(5):554–63.PubMedCrossRef
40.
Piulats JM, Matias-Guiu X. Immunotherapy in endometrial cancer: in the nick of time. Clin Cancer Res. 2016;22(23):5623–5.PubMedCrossRef
41.
Zhao D, Ren C, Yao Y et al. Identifying prognostic biomarkers in endometrial carcinoma based on ce RNA network. J Cell Biochem. 121(3): 2437–2446.
42.
Li Z, Yang HY, Zhang XL, et al. Kinesin family member 23, regulated by FOXM1, promotes triple negative breast cancer progression via activating Wnt/beta-catenin pathway. J Exp Clin Cancer Res. 2022;41(1):168.PubMedPubMedCentralCrossRef
43.
Yao DW, Song Q, He XZ. Kinesin family member 23 (KIF23) contributes to the progression of bladder cancer cells in vitro and in vivo. Neoplasma. 2021;68(2):298–306.PubMedCrossRef
44.
Chen J, Rajasekaran M, Xia H, et al. The microtubule-associated protein PRC1 promotes early recurrence of hepatocellular carcinoma in association with the Wnt/beta-catenin signalling pathway. Gut. 2016;65(9):1522–34.PubMedCrossRef
45.
Metadata
Title
Mechanism of regulation of KIF23 on endometrial cancer cell growth and apoptosis
Authors
Ruiying Zhuang
Haiyan Liu
Publication date
01-12-2024
Publisher
Springer US
Published in
Discover Oncology / Issue 1/2024
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI
https://doi.org/10.1007/s12672-024-00937-x

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