Dataset Information

KLF3 is a crucial regulator of metastasis by controlling STAT3 expression in lung cancer.

ABSTRACT: Lung cancer is one of the most common causes of cancer-related mortality worldwide, which is partially due to its metastasis. However, the mechanism underlying its metastasis remains elusive. In this study, we showed that a low Krüppel-like factor 3 (KLF3) expression level is correlated with a poor prognosis and TNM stages in clinical patients with lung cancer and further demonstrated that KLF3 expression is downregulated in lung cancer tissues compared with adjacent normal samples. In addition, bioinformatics analysis results showed that KLF3 expression is related to lung cancer epithelial-mesenchymal transition (EMT). In vitro and in vivo experiments also showed that KLF3 silencing promotes lung cancer EMT and enhances lung cancer metastasis. More importantly, bioinformatics analysis and in vitro experiments indicated that the role of KLF3 in lung cancer metastasis is dependent on the STAT3 signaling pathway. Overall, our data indicated the crucial function of KLF3 in lung cancer metastasis and suggested opportunities to improve the therapy of patients with lung cancer.

SUBMITTER: Sun W

PROVIDER: S-EPMC6852579 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

KLF3 is a crucial regulator of metastasis by controlling STAT3 expression in lung cancer.

Sun Wei W Hu Shan S Zu Yukun Y Deng Yu Y

Molecular carcinogenesis 20190905 11

Lung cancer is one of the most common causes of cancer-related mortality worldwide, which is partially due to its metastasis. However, the mechanism underlying its metastasis remains elusive. In this study, we showed that a low Krüppel-like factor 3 (KLF3) expression level is correlated with a poor prognosis and TNM stages in clinical patients with lung cancer and further demonstrated that KLF3 expression is downregulated in lung cancer tissues compared with adjacent normal samples. In addition, ...[more]

PMID: 31486564

Similar Datasets

Project description:Metastasis is the leading cause of mortality for human non-small cell lung cancer (NSCLC). However, it is difficult to target tumor metastasis because the molecular mechanisms underlying NSCLC invasion and migration remain unclear. Methods: GEO data analyses and IHC analyses were performed to identify that the expression level of AKR1C1, a member of human aldo-keto reductase family, was highly elevated in patients with metastasis or metastatic foci of NSCLC patients. Functional analyses (in vitro and in vivo) and quantitative genomic analyses were preformed to confirm the pro-metastatic effects of AKR1C1 and the underlying mechanisms. The correlation of AKR1C1 with the prognosis of NSCLC patients was evaluated using Kaplan-Meier analyses. Results: in NSCLC patients, AKR1C1 expression was closely correlated with the metastatic potential of tumors. AKR1C1 overexpression in nonmetastatic cancer cells significantly promoted metastasis both in vitro and in vivo, whereas depletion of AKR1C1 in highly metastatic tumors potently alleviated these effects. Quantitative genomic and functional analyses revealed that AKR1C1 directly interacted with STAT3 and facilitated its phosphorylation-thus reinforcing the binding of STAT3 to the promoter regions of target genes-and then transactivated these genes, which ultimately promoted tumor metastasis. Further studies showed that AKR1C1 might facilitate the interaction of STAT3 with its upstream kinase JAK2. Intriguingly, AKR1C1 exerted these pro-metastatic effects in a catalytic-independent manner. In addition, a significant correlation between AKR1C1 and STAT3 pathway was observed in the metastatic foci of NSCLC patients, and the AKR1C1-STAT3 levels were highly correlated with a poor prognosis in NSCLC patients. Conclusions: taken together, we show that AKR1C1 is a potent inducer of NSCLC metastasis. Our study uncovers the active function of AKR1C1 as a key component of the STAT3 pathway, which promotes lung cancer metastasis, and highlights a candidate therapeutic target to potentially improve the survival of NSCLC patients with metastatic disease.

Dataset Information

KLF3 is a crucial regulator of metastasis by controlling STAT3 expression in lung cancer.

Publications

KLF3 is a crucial regulator of metastasis by controlling STAT3 expression in lung cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets