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Article

Transcription Factor Eb Is Required for Macropinocytosis-Mediated Growth Recovery of Nutrient-Deprived Kras-Mutant Cells

1
Department of Biomedical Science, Kyungpook National University, Daegu 41566, Korea
2
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu 41566, Korea
3
New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea
4
Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Nutrients 2018, 10(11), 1638; https://doi.org/10.3390/nu10111638
Received: 22 October 2018 / Accepted: 26 October 2018 / Published: 2 November 2018
Macropinocytosis is a regulated form of endocytosis that mediates the nonselective uptake of nutrients to support growth under nutrient-deprived conditions. KRAS-mutant cancer cells upregulate macropinocytosis to import extracellular proteins, which subsequently undergo proteolytic degradation in the lysosome. Although transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and function, its role in the degradation of extracellular protein from macropinocytosis in KRAS-mutant cells has not previously been elucidated. In this study, we investigated the role of TFEB in the recovery of macropinocytosis-mediated mTORC1 activity and cell growth under nutrient depletion. Mouse embryonic fibroblasts (MEFs) expressing KrasG12D and KRAS-mutant human cancer cells took up markedly higher levels of tetramethylrhodamine (TMR)-dextran than the corresponding wild-type cells. siRNA-mediated inhibition of TFEB did not influence extracellular TMR-dextran uptake, but significantly attenuated lysosomal degradation of extracellular protein. Bovine serum albumin (BSA) treatment restored p-S6K levels and cell proliferation suppressed by leucine deprivation, and these effects were blocked by siTFEB. Collectively, our results show that TFEB plays a role in macropinocytosis-mediated KRAS-mutant cell growth under nutrient deprivation by promoting lysosomal degradation of extracellular proteins. View Full-Text
Keywords: KRAS; macropinocytosis; TFEB; lysosome KRAS; macropinocytosis; TFEB; lysosome
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MDPI and ACS Style

Jeong, S.; Byun, J.-K.; Cho, S.J.; Chin, J.; Lee, I.-K.; Choi, Y.-K.; Park, K.-G. Transcription Factor Eb Is Required for Macropinocytosis-Mediated Growth Recovery of Nutrient-Deprived Kras-Mutant Cells. Nutrients 2018, 10, 1638. https://doi.org/10.3390/nu10111638

AMA Style

Jeong S, Byun J-K, Cho SJ, Chin J, Lee I-K, Choi Y-K, Park K-G. Transcription Factor Eb Is Required for Macropinocytosis-Mediated Growth Recovery of Nutrient-Deprived Kras-Mutant Cells. Nutrients. 2018; 10(11):1638. https://doi.org/10.3390/nu10111638

Chicago/Turabian Style

Jeong, Seokmin, Jun-Kyu Byun, Sung Jin Cho, Jungwook Chin, In-Kyu Lee, Yeon-Kyung Choi, and Keun-Gyu Park. 2018. "Transcription Factor Eb Is Required for Macropinocytosis-Mediated Growth Recovery of Nutrient-Deprived Kras-Mutant Cells" Nutrients 10, no. 11: 1638. https://doi.org/10.3390/nu10111638

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