Abstract
BackgroundCCT3 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.MethodsCCT3 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.ResultsThe 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.ConclusionCCT3 is closely related to the proliferation and migration of breast cancer and may be a novel therapeutic target.
Highlights
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
We found that knockdown of CCT3 inhibits the proliferation and metastasis of breast cancer cells and that the mechanism is probably related to regulation of the cell cycle, apoptosis and several signal transduction pathways
Cells and materials HCC1937 and MDA-MB-231 cell lines were purchased from the Cell Bank of the Chinese Academy of Science (Shanghai, China); 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was purchased from Genview (Campbellfield, VIC, Australia); SYBR Master Mixture was purchased from Takara (Shimogyo-ku, Kyoto, Japan); antibodies against CCT3, CDH1, Slug, Snail, VIM, mTOR, ERK1/2, p-ERK1/2, p-AKT1, P38, p-P38, NFκB-65, p-NFκB-65, β-catenin and p-β-catenin were purchased from Cell Signaling Technology (Danvers, MA, USA); and antibodies against CDH2, MMP2, FN1, MYC, p-mTOR and AKT1 were purchased from Abcam (Cambridge, MA, USA)
Summary
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. The role of CCT3 in breast cancer is still unclear. Breast cancer is a common malignant tumour in women. The incidence rate of breast cancer is 24.2% worldwide. The mortality rate is the highest among malignant tumours, accounting for approximately 15% of cancer-related deaths in women [1]. The treatment of breast cancer mainly includes neoadjuvant therapy, surgery, chemotherapy, radiotherapy, targeted. Chaperonins are molecules that assist in the folding of newly synthesized and stress-denatured polypeptide chains and are divided into two groups, group I and group II. Heat shock protein 60 (HSP60) or GroEL in bacteria belongs to group I, and chaperonin-containing TCP-1 (CCT or TRiC) belongs to group II.
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