Transglutaminase 2 Promotes Autophagy by LC3 Induction through p53 Depletion in Cancer Cell.
10.4062/biomolther.2018.140
- Author:
Joon Hee KANG
1
;
Seon Hyeong LEE
;
Heesun CHEONG
;
Chang Hoon LEE
;
Soo Youl KIM
Author Information
1. Tumor Microenvironment Research Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang 10408, Republic of Korea. kimsooyoul@gmail.com
- Publication Type:Original Article
- Keywords:
Transglutaminase 2;
Autophagy;
LC3;
p53;
Cancer cell
- MeSH:
Autophagy*;
Carcinoma, Renal Cell;
Drug Resistance;
RNA, Small Interfering
- From:Biomolecules & Therapeutics
2019;27(1):34-40
- CountryRepublic of Korea
- Language:English
-
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.
