Open Access
ARTICLE
Phosphoglycerate Mutase 1 (PGAM1) Promotes Pancreatic Ductal Adenocarcinoma (PDAC) Metastasis by Acting as a Novel Downstream Target of the PI3K/Akt/mTOR Pathway
Xinlu Liu, Xiaodong Tan, Peng Liu, Yunhao Wu, Songying Qian, Xiaobo Zhang
First Department of General Surgery, Shengjing Hospital of China Medical University, Heping District,
Shenyang, Liaoning, P.R. China
Oncology Research 2018, 26(7), 1123-1131. https://doi.org/10.3727/096504018X15166223632406
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors known, with an overall 5-year
survival rate of less than 6% due to early local invasion and distant metastasis. Exploring suitable therapeutic targets associated with invasion and metastasis is required for improving the prognosis of PDAC. In this
study, we investigated the role of the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) in PDAC.
PGAM1 expression was examined in tissue samples of 54 PDAC patients using immunohistochemistry, and
the correlation between clinicopathological expression and PGAM1 expression was determined. A survival
curve was generated using the Kaplan–Meier method. After silencing PGAM1 by siRNA in pancreatic cancer cell lines Aspc-1 and Panc-1, the changes in proliferation, migration, and invasion, and signal pathways
were determined. In this study, the expression of PGAM1 was found positively related to poor differentiation,
metastasis, advanced clinical stage, and poor survival rate. Silencing PGAM1 decreased the proliferation of
Aspc-1 and Panc-1 cells with an S phase arrest, but without influencing cell apoptosis. Migration and invasion
also decreased significantly, independent of proliferation. PGAM1 was also found to promote EMT of PDAC
cell lines by regulating the Wnt/β-catenin pathway. PGAM1 itself was modulated by the PI3K/Akt/mTOR
pathway as a novel downstream target and has a positive mutual regulation with HIF-1a. This study indicates
that PGAM1 is closely associated with clinical metastasis and poor prognosis of PDAC. PGAM1 is considered
as a potential therapeutic target in PDAC metastasis.
Keywords
Cite This Article
APA Style
Liu, X., Tan, X., Liu, P., Wu, Y., Qian, S. et al. (2018). Phosphoglycerate mutase 1 (PGAM1) promotes pancreatic ductal adenocarcinoma (PDAC) metastasis by acting as a novel downstream target of the pi3k/akt/mtor pathway. Oncology Research, 26(7), 1123-1131. https://doi.org/10.3727/096504018X15166223632406
Vancouver Style
Liu X, Tan X, Liu P, Wu Y, Qian S, Zhang X. Phosphoglycerate mutase 1 (PGAM1) promotes pancreatic ductal adenocarcinoma (PDAC) metastasis by acting as a novel downstream target of the pi3k/akt/mtor pathway. Oncol Res. 2018;26(7):1123-1131 https://doi.org/10.3727/096504018X15166223632406
IEEE Style
X. Liu, X. Tan, P. Liu, Y. Wu, S. Qian, and X. Zhang "Phosphoglycerate Mutase 1 (PGAM1) Promotes Pancreatic Ductal Adenocarcinoma (PDAC) Metastasis by Acting as a Novel Downstream Target of the PI3K/Akt/mTOR Pathway," Oncol. Res., vol. 26, no. 7, pp. 1123-1131. 2018. https://doi.org/10.3727/096504018X15166223632406