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Upregulation of the oncogene carnitine palmitoyltransferase 1C under hypoxia requires HIF1
alpha and affects cell mobility
Ning Chang, Dorota Dudka, Daniel M. Aebersold, Jianhua Feng, and Kathrin Zaugg
Department of Radiation Oncology, Inselspital, Bern University Hospital and University of Bern,
Switzerland
Aim: We identified carnitine palmitoyltransferase 1C (CPT1C) as novel oncogene which is
regulated by hypoxia. Here we further investigate the requirement of HIF1 alpha in the regulation
of CPT1C. In addition, we examine the potential impact of CPT1C on cell migration, a crucial step
to facilitate cancer metastasis.
Methods: Mouse embryonic fibroblasts (MEF) from wildtype and HIF1 alpha null mice were
treated with normoxia or severe hypoxia (0.2 % oxygen) using either DMSO as control, a specific
HIF1 alpha inhibitor (KC7F2; 40 µM), ionizing irradiation (10 Gy) or etoposide as DNA damaging
reagent (10 µM). At various time points RNA and protein expression was measured by
quantitative PCR and western blotting, respectively. To determine the impact of CPT1C on cell
migration, HCT116 cells stably overexpressing CPT1C or MEFs depleted of CPT1C were subjected
to scratch assays and cell migration area was measured under the microscope.
Results: Under severe hypoxic conditions the oncogene CPT1C can only be upregulated when
both, the p53 and the HIF1 alpha pathway are activated. Interestingly, the induction of CPT1C by
ionizing irradiation or etoposide was not affected in HIF1 alpha null MEFs. Moreover,
overexpression of CPT1C in HCT116 cell decreased cell migration while depletion of CPT1C in MEF
cells increased cell migration.
Conclusion: Our results suggest HIF1 alpha is specifically required for the hypoxic induction of
CPT1C. Interestingly, expression of CPT1C leads to a decrease in cell migration. The knowledge
gained from this study provides new insights to better understand the oncogenic role of CPT1C.
Our data support our hypothesis that CPT1C might be a promising candidate to target hypoxic and
therefore treatment resistant cancers.