Journal
JOURNAL OF CANCER
Volume 9, Issue 23, Pages 4449-4462Publisher
IVYSPRING INT PUBL
DOI: 10.7150/jca.25926
Keywords
TNC; FOXO1; cell cycle; pancreatic cancer; proliferation
Categories
Funding
- National Natural Science Foundation of China [31370861]
- Tianjin Basic Research Plan Project [13JCZDJC31300]
Ask authors/readers for more resources
Pancreatic ductal adenocarcinoma (PDAC) is a disease with an extremely poor prognosis that is characterized by a rich extracellular matrix (ECM). Tenascin-C (TNC) is a component of the ECM and plays a role in tumour progression. In this study, we reported that TNC is overexpressed in PDAC tissues and is correlated with tumour stage and cyclin D1 expression. Cyclin D1 is key regulator of the cell cycle G1/S transition. Further experiments revealed that TNC promotes G1/S transition through AKT signalling. TNC/AKT increases the expression of cyclin D1 by enhancing the transcriptional activity of beta-catenin, whereas the translocation of FOXO1 from the nucleus results in the downregulation of p27(Kip1). Cyclin D1 and p27(Kip1) regulate the activity of cyclin D1-CDK4 complexes and retinoblastoma (Rb), and then they stimulate the progression of G1/S transition and tumour cell proliferation. In conclusion, TNC exerts its activating effect on the proliferation of pancreatic cancer cells in vitro and in vivo through its functional target AKT/FOXO1/beta-catenin. The molecular mechanisms that drive PDAC progression will be useful for the development of molecular markers and the evaluation of patient prognosis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available