Phosphoribosyl Pyrophosphate Amidotransferase Promotes the Progression of Thyroid Cancer via Regulating Pyruvate Kinase M2
Authors Liu B, Song M, Qin H, Zhang B, Liu Y, Sun Y, Ma Y, Shi T
Received 9 March 2020
Accepted for publication 17 June 2020
Published 3 August 2020 Volume 2020:13 Pages 7629—7639
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Cho
Bing Liu,1,* Meiyue Song,2,* Huadong Qin,1 Bin Zhang,1 Yao Liu,1 Yu Sun,1 Yanfei Ma,1 Tiefeng Shi1
1The 4th Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin City 150086, Heilongjiang Province, People’s Republic of China; 2The Pathology Department, The Second Affiliated Hospital of Harbin Medical University, Harbin City 150086, Heilongjiang Province, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Tiefeng Shi
The 4th Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, No. 246, Nangang District, Harbin City 150086, Heilongjiang Province, People’s Republic of China
Tel +86 451-86605419
Background: Pyruvate kinase is an enzyme that catalyzes the conversion of phosphoenolpyruvate and ADP to pyruvate and ATP in glycolysis and plays a role in regulating cell metabolism. It is reported that the activity of pyruvate kinase is increased in cancers. Phosphoribosyl amidotransferase (PPAT) is reported to be a crucial regulator for pyruvate kinase activity in lung cancer. However, its role in thyroid cancer remains largely unknown.
Materials and Methods: Immunohistochemical analysis and qRT-PCR were used to detect the expression of PPAT in thyroid cancer samples. Both gain-of-function and loss-of-function models were constructed in thyroid cancer cell lines and the biological functions of PPAT on cellular phenotypes were studied using CCK-8 assay and transwell assay in vitro, respectively. Then, Western blot was used to evaluate the change of PKM2 and downstream signal pathways after PPAT was overexpressed or knocked down.
Results: Immunohistochemical analysis showed increased expression of PPAT in thyroid cancer tissues, and it was associated with unfavorable pathological characteristics. Knockdown and overexpression assays suggested that altering PPAT expression modulated cell proliferation, migration, and invasion. In terms of mechanism, PPAT could positively regulate the expression of PKM2 and activate ERK and STAT3 signaling pathways.
Conclusion: PPAT plays crucial roles in regulating proliferation, migration, and invasion of thyroid cancer cells via activating PKM2, ERK, and STAT3.
Keywords: thyroid cancer, PPAT, PKM2, proliferation, migration, invasion
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