Keratin 17 knockdown suppressed malignancy and cisplatin tolerance of bladder cancer cells, as well as the activation of AKT and ERK pathway.
INTRODUCTION
Bladder cancer (BCa) is one the most common urinary system malignancies and approximately one quarter of diagnosis is invasive muscle-invasive BCa. Accumulating evidence revealed that keratin 17 (KRT17) is closely related to the prognosis and progression of various tumors including a recent study also implying the potential role of KRT17 in the diagnosis of BCa. However, the specific role of KRT17 in BCa remains to be elucidated.


MATERIAL AND METHODS
The expression of KRT17 in 5637 BCa cells and SV-HUC-1 normal human urothelial cells was detected using quantitative real-time PCR (qRT-PCR) and western blot. Short hairpin RNA targeting KRT17 was used to knockdown KRT17 in BCa cells. The colony formation was assessed and the proliferation of cells was studied by Cell Counting Kit-8 (CCK-8). Invasion and epithelial-mesenchymal transition (EMT) capacity of BCa cells were assessed using transwell assay and western blot, respectively. Cisplatin sensitivity of cancer cells was measured by evaluating the cell viability using CCK-8 assay. The downstream pathway of KRT17 was explored by western blot.


RESULTS
The expression of KRT17 was elevated in BCa cells in comparison with the normal human urothelial cell at the mRNA and protein levels. The in vitro assays demonstrated that KRT17 interference affected the proliferation, colony formation and invasion capacity of BCa cells, as well as EMT. Furthermore, knockdown of KRT17 enhanced cisplatin sensitivity in BCa cells. Mechanically, KRT17 ablation led to the inactivation of both AKT and ERK pathways.


CONCLUSIONS
Our results elucidate the vital role of KRT17 in the development of malignancy of BCa cells, probably by the activation of AKT and ERK pathways and suggest that it may represent a novel therapeutic target for BCa.
['Li|Chen|C|', 'Su|HongWei|H|', 'Ruan|CongGang|C|', 'Li|XiangDong|X|']
D045744:Cell Line, Tumor D049109:Cell Proliferation D002945:Cisplatin D019008:Drug Resistance, Neoplasm D058750:Epithelial-Mesenchymal Transition D055785:Gene Knockdown Techniques D006801:Humans D053537:Keratin-17 D020935:MAP Kinase Signaling System D015854:Up-Regulation D001749:Urinary Bladder Neoplasms
keratin 17 bladder cancer AKT ERK invasion proliferation EMT cisplatin sensitivity 5637 cells SV-HUC-1 cells shRNA