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Tytuł pozycji:

CDK5 neutralizes the tumor suppressing effect of BIN1 via mediating phosphorylation of c-MYC at Ser-62 site in NSCLC

Tytuł :
CDK5 neutralizes the tumor suppressing effect of BIN1 via mediating phosphorylation of c-MYC at Ser-62 site in NSCLC
Autorzy :
Xiangyu Zhang
Jiali Wang
Yunlong Jia
Tianxu Liu
Mengjie Wang
Wei Lv
Rong Zhang
Juan Shi
Lihua Liu
Pokaż więcej
Temat :
CDK5
BIN1
c-MYC
NSCLC
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Cytology
QH573-671
Źródło :
Cancer Cell International, Vol 19, Iss 1, Pp 1-12 (2019)
Wydawca :
BMC, 2019.
Rok publikacji :
2019
Kolekcja :
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
LCC:Cytology
Typ dokumentu :
article
Opis pliku :
electronic resource
Język :
English
ISSN :
1475-2867
Relacje :
http://link.springer.com/article/10.1186/s12935-019-0952-5; https://doaj.org/toc/1475-2867
DOI :
10.1186/s12935-019-0952-5
Dostęp URL :
https://doaj.org/article/775b58f4d6ee492aaa7e4d81594326ae
Numer akcesji :
edsdoj.775b58f4d6ee492aaa7e4d81594326ae
Czasopismo naukowe
Abstract Background Bridging integrator 1 (BIN1) has showed outstanding tumor-suppressive potential via inhibiting c-MYC-mediated tumorigenesis. However, a frequent phosphorylation of c-MYC at Ser-62 site could block the BIN1/c-MYC interaction and limits the tumor-suppressive effect of BIN1. Cyclin-dependent kinase 5 (CDK5), a generally dysregulated protein in various carcinomas, can mediate c-MYC phosphorylation at Ser-62 site. However, whether the existence of CDK5 could block the BIN1/c-MYC interaction remains unclear. Materials and methods The expression of CDK5 and BIN1 in non-small cell lung cancer (NSCLC) cell lines were measured. CDK5 was knocked down and overexpressed in H460 and PC9 cells, respectively. CCK-8, wound healing and transwell were used to detect the proliferation, migration and invasion ability of NSCLC cells. Tumor-bearing nude mouse model was built with H460 cells. Dinaciclib was added to realize the effect of CDK5 inhibition in vivo. NSCLC and matched para-carcinoma specimens were collected from 153 patients who underwent radical operation. IHC was performed to determine the expression of CDK5 in the specimens. Kaplan–Meier analysis was used to analyze the correlation between the postoperative survival and CDK5 expression. Results CDK5 was highly expressed in H460 cells, and knockdown of CDK5 could restore the BIN1/c-MYC interaction. Meanwhile, low expression of CDK5 was observed in PC9 cells, and overexpression of CDK5 blocked the BIN1/c-MYC interaction. Consequently, the growth, migration, invasion and epithelial mesenchymal transition (EMT) ability of H460 and PC9 cells could be facilitated by CDK5. The addition of CDK5 inhibitor Dinaciclib significantly suppressed the tumorigenesis ability of NSCLC cells in tumor-bearing mouse model. Furthermore, high expression of CDK5, along with low expression of BIN1, could predict poor postoperative prognosis of NSCLC patients. The patients with high expression of CDK5 and low expression of BIN1 showed similar prognosis, indicating that CDK5 could neutralize the tumor suppressing effect of BIN1 in clinical situation. Conclusions CDK5 blocked the interaction of BIN1 and c-MYC via promoting phosphorylation of c-MYC at ser-62 site, ultimately facilitated the progression of NSCLC.
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