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| Status |
Public on Sep 23, 2019 |
| Title |
Loss of thymidine kinase 1 inhibits lung cancer growth and metastatic attributes by reducing GDF15 expression |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Metabolic alterations that are critical for cancer cell growth and metastasis are one of the key hallmarks of cancer. Here, we show that thymidine kinase 1 (TK1) is significantly overexpressed in tumor samples from lung adenocarcinoma (LUAD) patients relative to normal controls, and this TK1 overexpression is associated with significantly reduced overall survival and cancer recurrence. Genetic knockdown of TK1 with short hairpin RNAs (shRNAs) inhibits both the growth and metastatic attributes of LUAD cells in culture and in mice. We further show that transcriptional overexpression of TK1 in LUAD cells is driven, in part, by MAP kinase pathway in a transcription factor MAZ dependent manner. Using targeted and gene expression profiling-based approaches, we then show that loss of TK1 in LUAD cells results in reduced Rho GTPase activity and reduced expression of growth and differentiation factor 15 (GDF15). Furthermore, ectopic expression of GDF15 can partially rescue TK1 knockdown-induced LUAD growth and metastasis inhibition, confirming its important role as a downstream mediator of TK1 function in LUAD. Collectively, our findings demonstrate that TK1 facilitates LUAD tumor and metastatic growth and represents a target for LUAD therapy.
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| Overall design |
A549 cells stably expressing two individual shRNAs against TK1 or as a control A549 cells expressing non-specific shRNAs were used to prepare the total RNA, which was then used to analyze for gene expression using Illumina HumanHT-12 V4.0 expression beadchip
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| Contributor(s) |
Malvi P, Wajapeyee N |
| Citation(s) |
31589613 |
| |
| Submission date |
Nov 23, 2016 |
| Last update date |
Dec 20, 2021 |
| Contact name |
Narendra Wajapeyee |
| E-mail(s) |
nwajapey@uab.edu
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| Phone |
205-934-5331
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| Organization name |
University of Alabama at Birmingham
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| Department |
Department of Biochemistry and Molecular Genetics
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| Street address |
720 20th Street South, Kaul 540A
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| City |
Birmingham |
| State/province |
AL |
| ZIP/Postal code |
35233 |
| Country |
USA |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA354812 |
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