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http://dx.doi.org/10.4062/biomolther.2018.140

Transglutaminase 2 Promotes Autophagy by LC3 Induction through p53 Depletion in Cancer Cell  

Kang, Joon Hee (Tumor Microenvironment Research Branch, Division of Cancer Biology, Research Institute, National Cancer Center)
Lee, Seon-Hyeong (Tumor Microenvironment Research Branch, Division of Cancer Biology, Research Institute, National Cancer Center)
Cheong, Heesun (Tumor Microenvironment Research Branch, Division of Cancer Biology, Research Institute, National Cancer Center)
Lee, Chang Hoon (College of Pharmacy, Dongguk University)
Kim, Soo-Youl (Tumor Microenvironment Research Branch, Division of Cancer Biology, Research Institute, National Cancer Center)
Publication Information
Biomolecules & Therapeutics / v.27, no.1, 2019 , pp. 34-40 More about this Journal
Abstract
Transglutaminase 2 (TGase 2) plays a key role in p53 regulation, depleting p53 tumor suppressor through autophagy in renal cell carcinoma. We found that microtubule-associated protein 1A/1B-light chain 3 (LC3), a hallmark of autophagy, were tightly associated with the level of TGase 2 in cancer cells. TGase 2 overexpression increased LC3 levels, and TGase 2 knockdown decreased LC3 levels in cancer cells. Transcript abundance of LC3 was inversely correlated with level of wild type p53. TGase 2 knockdown using siRNA, or TGase 2 inhibition using GK921 significantly reduced autophagy through reduction of LC3 transcription, which was followed by restoration of p53 levels in cancer cells. TGase 2 overexpression promoted the autophagy process by LC3 induction, which was correlated with p53 depletion in cancer cells. Rapamycin-resistant cancer cells also showed higher expression of LC3 compared to the rapamycin-sensitive cancer cells, which was tightly correlated with TGase 2 levels. TGase 2 knockdown or TGase 2 inhibition sensitized rapamycin-resistant cancer cells to drug treatment. In summary, TGase 2 induces drug resistance by potentiating autophagy through LC3 induction via p53 regulation in cancer.
Keywords
Transglutaminase 2; Autophagy; LC3; p53; Cancer cell;
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