Skip to main content
Top
Published in: Cancer Cell International 1/2020

01-12-2020 | Metastasis | Primary research

Suppression of CCT3 inhibits the proliferation and migration in breast cancer cells

Authors: Gang Xu, Shanshan Bu, Xiushen Wang, He Zhang, Hong Ge

Published in: Cancer Cell International | Issue 1/2020

Login to get access

Abstract

Background

CCT3 is a subunit of chaperonin-containing TCP-1 (CCT), which folds many proteins involved in cancer development and plays an important role in many cancers. However, the role of CCT3 in breast cancer is still unclear.

Methods

CCT3 expression was knocked down by transfecting breast cancer cells with lentiviral shRNA. The proliferation of breast cancer cells (HCC1937 and MDA-MB-231) was detected by Celigo image cytometry and MTT assay, the migration of the cells was measured by Transwell analysis, cell cycle distribution and apoptosis was detected by flow cytometry, and changes in signal transduction proteins were detected by western blot analysis.

Results

The expression of CCT3 was significantly suppressed by transduction with lentiviral shRNA; CCT3 knockdown significantly reduced the proliferation and metastasis ability of breast cancer cells (HCC 1937 and MDA-MB-231), increased the proportion of cells in S phase, and decreased the proportion of cells in G1 phase compared to those in shControl cells. There was no significant change in the number of cells in the G2/M phase. Apoptosis analysis showed that knockdown of CCT3 induced apoptosis in breast cancer cells. Western blot analysis showed that the expression of many signal transduction proteins was changed after suppression of CCT3. A rescue experiment showed that overexpression of NFκB-p65 rescued the cell proliferation and migration affected by CCT3 in breast cancer cells.

Conclusion

CCT3 is closely related to the proliferation and migration of breast cancer and may be a novel therapeutic target.
Literature
4.
go back to reference Stoldt V, Rademacher F, Kehren V, Ernst JF, Pearce DA, Sherman F. Review: the CCT eukaryotic chaperonin subunits of Saccharomyces cerevisiae and other yeasts. Yeast. 1996;12:523–9.CrossRef Stoldt V, Rademacher F, Kehren V, Ernst JF, Pearce DA, Sherman F. Review: the CCT eukaryotic chaperonin subunits of Saccharomyces cerevisiae and other yeasts. Yeast. 1996;12:523–9.CrossRef
5.
go back to reference Valpuesta JM, Martin-Benito J, Gomez-Puertas P, Carrascosa JL, Willison KR. Structure and function of a protein folding machine: the eukaryotic cytosolic chaperonin CCT. FEBS Lett. 2002;529:11–6.CrossRef Valpuesta JM, Martin-Benito J, Gomez-Puertas P, Carrascosa JL, Willison KR. Structure and function of a protein folding machine: the eukaryotic cytosolic chaperonin CCT. FEBS Lett. 2002;529:11–6.CrossRef
6.
go back to reference Karen IB, Julie G. Activities of the chaperonin containing TCP-1 (CCT): implications for cell cycle progression and cytoskeletal organisation. Cell Stress Chaperones. 2009;14(1):23–31.CrossRef Karen IB, Julie G. Activities of the chaperonin containing TCP-1 (CCT): implications for cell cycle progression and cytoskeletal organisation. Cell Stress Chaperones. 2009;14(1):23–31.CrossRef
8.
go back to reference Hou Jia-Yin, Hua-Yu Wu, He Rong-Quan, Lin Peng, Dang Yi-Wu, Chen Gang. Clinical and prognostic value of chaperonin containing T-complex 1 subunit 3 in hepatocellular carcinoma: a study based on microarray and RNA-sequencing with 4272 cases. Pathol Res Pract. 2019;215(1):177–94.CrossRef Hou Jia-Yin, Hua-Yu Wu, He Rong-Quan, Lin Peng, Dang Yi-Wu, Chen Gang. Clinical and prognostic value of chaperonin containing T-complex 1 subunit 3 in hepatocellular carcinoma: a study based on microarray and RNA-sequencing with 4272 cases. Pathol Res Pract. 2019;215(1):177–94.CrossRef
9.
go back to reference Zhang Y, Wang Y, Wei Y, Wu J, Zhang P, Shen S, Saiyin H, Wumaier R, Yang X, Wang C, et al. Molecular chaperone CCT3 supports proper mitotic progression and cell proliferation in hepatocellular carcinoma cells. Cancer Lett. 2016;372(1):101–9.CrossRef Zhang Y, Wang Y, Wei Y, Wu J, Zhang P, Shen S, Saiyin H, Wumaier R, Yang X, Wang C, et al. Molecular chaperone CCT3 supports proper mitotic progression and cell proliferation in hepatocellular carcinoma cells. Cancer Lett. 2016;372(1):101–9.CrossRef
10.
go back to reference Li LJ, Zhang LS, Han ZJ, He ZY, Chen H, Li YM. Chaperonin containing TCP-1 subunit 3 is critical for gastric cancer growth. Oncotarget. 2017;8(67):111470–81.CrossRef Li LJ, Zhang LS, Han ZJ, He ZY, Chen H, Li YM. Chaperonin containing TCP-1 subunit 3 is critical for gastric cancer growth. Oncotarget. 2017;8(67):111470–81.CrossRef
11.
go back to reference Shi XH, Cheng SS, Wang WX. Suppression of CCT3 inhibits malignant proliferation of human papillary thyroid carcinoma cell. Oncol Lett. 2018;15(6):9202–8.PubMedPubMedCentral Shi XH, Cheng SS, Wang WX. Suppression of CCT3 inhibits malignant proliferation of human papillary thyroid carcinoma cell. Oncol Lett. 2018;15(6):9202–8.PubMedPubMedCentral
20.
go back to reference Olson MF, Sahai E. The actin cytoskeleton in cancer cell motility. Clin Exp Metastasis. 2009;26:273–87.CrossRef Olson MF, Sahai E. The actin cytoskeleton in cancer cell motility. Clin Exp Metastasis. 2009;26:273–87.CrossRef
21.
go back to reference Zhao M, Spiess M, Johansson HJ, Olofsson H, Hu J, Lehtio J, Stromblad S. Identification of the PAK4 interactome reveals PAK4 phosphorylation of N-WASP and promotion of Arp2/3-dependent actin polymerization. Oncotarget. 2017;8:77061–74.CrossRef Zhao M, Spiess M, Johansson HJ, Olofsson H, Hu J, Lehtio J, Stromblad S. Identification of the PAK4 interactome reveals PAK4 phosphorylation of N-WASP and promotion of Arp2/3-dependent actin polymerization. Oncotarget. 2017;8:77061–74.CrossRef
22.
go back to reference Brackley KI, Grantham J. Interactions between the actin filament capping and severing protein gelsolin and the molecular chaperone CCT: evidence for nonclassical substrate interactions. Cell Stress Chaperones. 2011;16:173–9.CrossRef Brackley KI, Grantham J. Interactions between the actin filament capping and severing protein gelsolin and the molecular chaperone CCT: evidence for nonclassical substrate interactions. Cell Stress Chaperones. 2011;16:173–9.CrossRef
25.
go back to reference Yang X, Ren H, Shao Y, Sun Y, Zhang L, Li H, Zhang X, Yang X, Yu W, Fu J. Chaperonin-containing T-complex protein 1 subunit 8 promotes cell migration and invasion in human esophageal squamous cell carcinoma by regulating α-actin and β-tubulin expression. Int J Oncol. 2018;52(6):2021–30. https://doi.org/10.3892/ijo.2018.4335.CrossRefPubMed Yang X, Ren H, Shao Y, Sun Y, Zhang L, Li H, Zhang X, Yang X, Yu W, Fu J. Chaperonin-containing T-complex protein 1 subunit 8 promotes cell migration and invasion in human esophageal squamous cell carcinoma by regulating α-actin and β-tubulin expression. Int J Oncol. 2018;52(6):2021–30. https://​doi.​org/​10.​3892/​ijo.​2018.​4335.CrossRefPubMed
27.
go back to reference Yokota S, Yanagi H, Yura T, Kubota H. Cytosolic chaperonin is upregulated during cell growth. Preferential expression and binding to tubulin at G(1)/S transition through early S phase. J Biol Chem. 1999;274:37070–8.CrossRef Yokota S, Yanagi H, Yura T, Kubota H. Cytosolic chaperonin is upregulated during cell growth. Preferential expression and binding to tubulin at G(1)/S transition through early S phase. J Biol Chem. 1999;274:37070–8.CrossRef
28.
go back to reference Camasses A, Bogdanova A, Shevchenko A, Zachariae W. The CCT chaperonin promotes activation of the anaphase-promoting complex through the generation of functional Cdc20. Mol Cell. 2003;12:87–100.CrossRef Camasses A, Bogdanova A, Shevchenko A, Zachariae W. The CCT chaperonin promotes activation of the anaphase-promoting complex through the generation of functional Cdc20. Mol Cell. 2003;12:87–100.CrossRef
Metadata
Title
Suppression of CCT3 inhibits the proliferation and migration in breast cancer cells
Authors
Gang Xu
Shanshan Bu
Xiushen Wang
He Zhang
Hong Ge
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01314-8

Other articles of this Issue 1/2020

Cancer Cell International 1/2020 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine