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The adaptive regulation of thiamine pyrophosphokinase-1 facilitates malignant growth during supplemental thiamine conditions.
Authors: Jonus HC, Hanberry BS, Khatu S, Kim J, Luesch H, Dang LH, Bartlett MG, Zastre JA Abstract Supplemental levels of vitamin B1 (thiamine) have been implicated in tumor progression. Tumor cells adaptively up-regulate thiamine transport during hypoxic stress. Upon uptake, thiamine pyrophosphokinase-1 (TPK1) facilitates the rapid phosphorylation of thiamine into thiamine pyrophosphate (TPP). However, the regulation of TPK1 during hypoxic stress is undefined. Understanding how thiamine homeostasis changes during hypoxia will provide critical insight into the malignant advantage supplemental thiamine may provide c...
Source: Oncotarget - November 22, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Identification of vitamin B1 metabolism as a tumor-specific radiosensitizing pathway using a high-throughput colony formation screen.
Authors: Tiwana GS, Prevo R, Buffa FM, Yu S, Ebner DV, Howarth A, Folkes LK, Budwal B, Chu KY, Durrant L, Muschel RJ, McKenna WG, Higgins GS Abstract Colony formation is the gold standard assay for determining reproductive cell death after radiation treatment, since effects on proliferation often do not reflect survival. We have developed a high-throughput radiosensitivity screening method based on clonogenicity and screened a siRNA library against kinases. Thiamine pyrophosphokinase-1 (TPK1), a key component of Vitamin B1/thiamine metabolism, was identified as a target for radiosensitization. TPK1 knockdown caused...
Source: Oncotarget - March 22, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research