Abstract
Introduction
KIFC3 is a member of the kinesin family which has shown great promise in cancer therapy
recently. In this study, we sought to elucidate the role of KIFC3 in the development
of GC and its possible mechanisms.
Methods
Two databases and a tissue microarray were used to explore the expression of KIFC3
and its correlation with patients’ clinicopathological characteristics. Cell proliferation
was examined by cell counting kit-8 assay and colony formation assay. Wound healing
assay and transwell assay were performed to examine cell metastasis ability. EMT and
Notch signaling related proteins were detected by western blot. Additionally, a xenograft
tumor model was established to investigate the function of KIFC3 in vivo.
Results
The expression of KIFC3 was upregulated in GC, and was associated with higher T stage
and poor prognosis in GC patients. The proliferation and metastasis ability of GC
cells were promoted by KIFC3 overexpression while inhibited by KIFC3 knockdown in
vitro and in vivo. Furthermore, KIFC3 might activate the Notch1 pathway to facilitate
the progression of GC, and DAPT, an inhibitor of Notch signaling, could reverse this
effect.
Conclusion
Together, our data revealed that KIFC3 could enhance the progression and metastasis
of GC by activating the Notch1 pathway.
Keywords
Abbreviations:
GC (gastric cancer), KIFs (kinesin superfamily proteins), EMT (epithelial-mesenchymal transition), ADAM (an disintegrin and metalloproteinase domain-containing protein), TCGA (The Cancer Genome Atlas), IHC (immunohistochemistry), GSI (γ-secretase inhibitor)To read this article in full you will need to make a payment
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References
- Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin. 2021; 71: 209-249
- Burden of gastric cancer.Clinic. Gastroenterol. Hepatol. 2020; 18: 534-542
- All kinesin superfamily protein, KIF, genes in mouse and human.Proc. Natl. Acad. Sci. U.S.A. 2001; 98: 7004-7011
- Kinesin superfamily proteins and their various functions and dynamics.Exp. Cell Res. 2004; 301: 50-59
- Functional analysis of human microtubule-based motor proteins, the kinesins and dyneins, in mitosis/cytokinesis using RNA interference.Mol. Biol. Cell. 2005; 16: 3187-3199
- Kinesinopathies': emerging role of the kinesin family member genes in birth defects.J. Med. Genet. 2020; 57: 797-807
- Overexpression of kinesin superfamily members as prognostic biomarkers of breast cancer.Cancer Cell Int. 2020; 20: 123
- Identification of key genes in invasive clinically non-functioning pituitary adenoma by integrating analysis of DNA methylation and mRNA expression profiles.J. Transl. Med. 2019; 17: 407
- KIFC3 promotes proliferation, migration and invasion of esophageal squamous cell carcinoma cells by activating EMT and β-catenin signaling.World J. Gastrointest. Oncol. 2022; 14: 1239-1251
- KIFC3 promotes proliferation, migration, and invasion in colorectal cancer via PI3K/AKT/mTOR signaling pathway.Front. Genet. 2022; 13848926
- Biophysics of Notch signaling.Annu. Rev. Biophys. 2021; 50: 157-189
- The varied roles of Notch in cancer.Annu. Rev. Pathol. 2017; 12: 245-275
- Notch signaling in stomach epithelial stem cell homeostasis.J. Exp. Med. 2011; 208: 677-688
- Notch as a driver of gastric epithelial cell proliferation.Cell Mol. Gastroenterol. Hepatol. 2017; 3: 323-330
- Molecular classification of gastric cancer.Ann. Oncol. 2016; 27: 763-769
- Gastric cancer: a comprehensive review of current and future treatment strategies.Cancer Metastasis Rev. 2020; 39: 1179-1203
- KIFC1 is a novel potential therapeutic target for breast cancer.Cancer Biol. Ther. 2015; 16: 1316-1322
- KIFC1, a novel potential prognostic factor and therapeutic target in hepatocellular carcinoma.Int. J. Oncol. 2018; 52: 1912-1922
- The overexpression of KIFC1 was associated with the proliferation and prognosis of non-small cell lung cancer.J. Thorac. Dis. 2016; 8: 2911-2923
- High KIFC1 expression is associated with poor prognosis in prostate cancer.Med. Oncol. 2021; 38: 47
- KIF14 mRNA expression is a predictor of grade and outcome in breast cancer.Int. J. Cancer. 2006; 119: 1088-1094
- KIF14 messenger RNA expression is independently prognostic for outcome in lung cancer.Clinic. Cancer Res. 2007; 13: 3229-3234
- MiR-19a/miR-96-mediated low expression of KIF26A suppresses metastasis by regulating FAK pathway in gastric cancer.Oncogene. 2021; 40: 2524-2538
- KIF26B, a novel oncogene, promotes proliferation and metastasis by activating the VEGF pathway in gastric cancer.Oncogene. 2017; 36: 5609-5619
- KIF15 promotes the evolution of gastric cancer cells through inhibition of reactive oxygen species-mediated apoptosis.J. Cell. Physiol. 2020; 235: 9388-9398
- Effect of KIF22 on promoting proliferation and migration of gastric cancer cells via MAPK-ERK pathways.Chin. Med. J. 2020; 133: 919-928
- KIF23 Promotes Gastric Cancer by Stimulating Cell Proliferation.Dis. Markers. 2019; 20199751923
- Kinesin family member 2A links with advanced tumor stage, reduced chemosensitivity and worse prognosis in gastric cancer.J. Clin. Lab. Anal. 2022; 36: e24313
- Targeting kinesin family member 21B by miR-132-3p represses cell proliferation, migration and invasion in gastric cancer.Bioengineered. 2022; 13: 9006-9018
- Inhibition of the mitotic kinesin Eg5 up-regulates Hsp70 through the phosphatidylinositol 3-kinase/Akt pathway in multiple myeloma cells.J. Biol. Chem. 2006; 281: 18090-18097
- A phase 1 dose-escalation study of filanesib plus bortezomib and dexamethasone in patients with recurrent/refractory multiple myeloma.Cancer. 2016; 122: 3327-3335
- The balance between KIFC3 and EG5 tetrameric kinesins controls the onset of mitotic spindle assembly.Nat. Cell Biol. 2019; 21: 1138-1151
- Defective recruitment of motor proteins to autophagic compartments contributes to autophagic failure in aging.Aging Cell. 2018; 17: e12777
- Microtubule minus-end binding protein CAMSAP2 and Kinesin-14 Motor KIFC3 control dendritic microtubule organization.Curr. Biol. 2020; 30 (899-908 e896)
- Prognostic values of four Notch receptor mRNA expression in gastric cancer.Sci. Rep. 2016; 6: 28044
- Notch1 activation is a poor prognostic factor in patients with gastric cancer.Br. J. Cancer. 2014; 110: 2283-2290
- Activation of the Notch1/STAT3/Twist signaling axis promotes gastric cancer progression.Carcinogenesis. 2012; 33: 1459-1467
- The activated Notch1 signal pathway is associated with gastric cancer progression through cyclooxygenase-2.Cancer Res. 2009; 69: 5039-5048
- Over-activated Notch-1 protects gastric carcinoma BGC-823 cells from TNFalpha-induced apoptosis.Dig. Liver Dis. 2009; 41: 867-874
- The molecular mechanism of kinesin family member 2A (KIF2A) underlying non-small cell lung cancer: the effect of its knockdown on malignant behaviors, stemness, chemosensitivity, and potential regulated signaling pathways.Am. J. Transl. Res. 2022; 14: 68-85
- Notch and Wnt signals cooperatively control cell proliferation and tumorigenesis in the intestine.Proc. Natl. Acad. Sci. U.S.A. 2009; 106: 6309-6314
- Jagged2 progressively increased expression from Stage I to III of bladder cancer and melatonin-mediated downregulation of Notch/Jagged2 suppresses the Bladder Tumorigenesis via inhibiting PI3K/AKT/mTOR/MMPs signaling.Int. J. Biol. Sci. 2020; 16: 2648-2662
Article info
Publication history
Published online: March 06, 2023
Accepted:
February 14,
2023
Received:
November 9,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l.
