Title
Downregulation of Bit1 Expression Promotes Growth, Anoikis Resistance, and Transformation of Immortalized Human Bronchial Epithelial Cells via Erk Activation-Dependent Suppression of E-cadherin.
Funding Source
Xavier University of Louisiana, National Institutes of Health
Grant Number
R25GM060926, 8G12MD007595,2R15 CA158677-02
Department
Department of Biology
Document Type
Article
Publication Date
1-2018
Abstract
The mitochondrial Bit1 protein exerts tumor-suppressive function in NSCLC through induction of anoikis and inhibition of EMT. Having this dual tumor suppressive effect, its downregulation in the established human lung adenocarcinoma A549 cell line resulted in potentiation of tumorigenicity and metastasis in vivo. However, the exact role of Bit1 in regulating malignant growth and transformation of human lung epithelial cells, which are origin of most forms of human lung cancers, has not been examined. To this end, we have downregulated the endogenous Bit1 expression in the immortalized non-tumorigenic human bronchial epithelial BEAS-2B cells. Knockdown of Bit1 enhanced the growth and anoikis insensitivity of BEAS-2B cells. In line with their acquired anoikis resistance, the Bit1 knockdown BEAS-2B cells exhibited enhanced anchorage-independent growth in vitro but failed to form tumors in vivo. The loss of Bit1-induced transformed phenotypes was in part attributable to the repression of E-cadherin expression since forced exogenous E-cadherin expression attenuated the malignant phenotypes of the Bit1 knockdown cells. Importantly, we show that the loss of Bit1 expression in BEAS-2B cells resulted in increased Erk activation, which functions upstream to promote TLE1-mediated transcriptional repression of E-cadherin. These collective findings indicate that loss of Bit1 expression contributes to the acquisition of malignant phenotype of human lung epithelial cells via Erk activation-induced suppression of E-cadherin expression.
Recommended Citation
Yao, Xin; Gray, S.; Pham, T.; Delgardo, M.; Nguyen, A.; Do, S.; Ireland, Shubha Kale; Chen, R.; Abdel-Mageed, A. B.; and Biliran, Hector, "Downregulation of Bit1 Expression Promotes Growth, Anoikis Resistance, and Transformation of Immortalized Human Bronchial Epithelial Cells via Erk Activation-Dependent Suppression of E-cadherin." (2018). Faculty and Staff Publications. 212.
https://digitalcommons.xula.edu/fac_pub/212
Comments
DOI: 10.1016/j.bbrc.2017.11.126
PubMed ID: 29170133
Funding text
This work was supported by the Louisiana Cancer Research Consortium start up grant (to HB), NIH 2R15 CA158677-02 Grant (to HB), NIH RCMI grant # 8G12MD007595 (Xavier University of Louisiana), and NIH R25GM060926 (Xavier University of Louisiana).