title: Downregulation of CDC27 inhibits the proliferation of colorectal cancer cells via the accumulation of p21Cip1/Waf1.
abstract: Dysregulated cell cycle progression has a critical role in tumorigenesis. Cell division cycle 27 (CDC27) is a core subunit of the anaphase-promoting complex/cyclosome, although the specific role of CDC27 in cancer remains unknown. In our study, we explored the biological and clinical significance of CDC27 in colorectal cancer (CRC) growth and progression and investigated the underlying molecular mechanisms. Results showed that CDC27 expression is significantly correlated with tumor progression and poor patient survival. Functional assays demonstrated that overexpression of CDC27 promoted proliferation in DLD1 cells, whereas knockdown of CDC27 in HCT116 cells inhibited proliferation both in vitro and in vivo. Further mechanistic investigation showed that CDC27 downregulation resulted in G1/S phase transition arrest via the significant accumulation of p21 in HCT116 cells, and the upregulation of CDC27 promoted G1/S phase transition via the attenuation of p21 in DLD1 cells. Furthermore, we also demonstrated that CDC27 regulated inhibitor of DNA binding 1 (ID1) protein expression in DLD1 and HCT116 cells, and rescue assays revealed that CDC27 regulated p21 expression through modulating ID1 expression. Taken together, our results indicate that CDC27 contributes to CRC cell proliferation via the modulation of ID1-mediated p21 regulation, which offers a novel approach to the inhibition of tumor growth. Indeed, these findings provide new perspectives for the future study of CDC27 as a target for CRC treatment.
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: L
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.affiliation: Medical Oncology, Sichuan Cancer Hospital and Institute, Second People's Hospital of Sichuan Province, Chengdu, China.
authors.forename: C
authors.initials: C
authors.lastname: Pan
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Tan
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Lin
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: R
authors.initials: R
authors.lastname: Liu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: R
authors.initials: R
authors.lastname: Geng
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors.forename: W
authors.initials: W
authors.lastname: Huang
mesh_terms: D000818:Animals; D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D018450:Disease Progression; D015536:Down-Regulation; D045325:HCT116 Cells; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014162:Transfection
chemical_list: D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; C577366:CDC27 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21
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