Nitrilase 1 modulates lung tumor progression in vitro and in vivo.
Publication/Presentation Date
4-19-2016
Abstract
Uncovering novel growth modulators for non-small cell lung cancer (NSCLC) may lead to new therapies for these patients. Previous studies suggest Nit1 suppresses chemically induced carcinogenesis of the foregut in a mouse model. In this study we aimed to determine the role of Nit1 in a transgenic mouse lung cancer model driven by a G12D Kras mutation. Nit1 knockout mice (Nit1-/-) were crossed with KrasG12D/+ mice to investigate whether a G12D Kras mutation and Nit1 inactivation interact to promote or inhibit the development of NSCLC. We found that lung tumorigenesis was suppressed in the Nit1-null background (Nit1-/-:KrasG12D/+). Micro-CT scans and gross tumor measurements demonstrated a 5-fold reduction in total tumor volumes compared to Nit1+/+KrasG12D/+ (p< 0.01). Furthermore, we found that Nit1 is highly expressed in human lung cancer tissues and cell lines and use of siRNA against Nit1 decreased overall cell survival of lung cancer cells in culture. In addition, cisplatin response was enhanced in human lung cancer cells when Nit1 was knocked down and Nit1-/-:KrasG12D/+ tumors showed increased sensitivity to cisplatin in vivo. Together, our data indicate that Nit1 may play a supportive role in the modulation of lung tumorigenesis and represent a novel target for NSCLCs treatment.
Volume
7
Issue
16
First Page
21381
Last Page
21392
ISSN
1949-2553
Published In/Presented At
Wang, Y. A., Sun, Y., Le Blanc, J. M., Solomides, C., Zhan, T., & Lu, B. (2016). Nitrilase 1 modulates lung tumor progression in vitro and in vivo. Oncotarget, 7(16), 21381–21392. https://doi.org/10.18632/oncotarget.7820
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
26967383
Department(s)
Administration and Leadership
Document Type
Article