PKM2 regulates hepatocellular carcinoma cell epithelial-mesenchymal transition and migration upon EGFR activation.
Pyruvate kinase isozyme type M2(PKM2) was first found in hepatocellular carcinoma(HCC), and its expression has been thought to correlate with prognosis. A large number of studies have demonstrated that epithelial-mesenchymal transition (EMT) is a crucial event in hepatocellular carcinoma (HCC) and associated metastasis, resulting in enhanced malignancy of HCC. However, the roles of PKM2 in HCC EMT and metastasis remain largely unknown. The present study aimed to determine the effects of PKM2 in EGF-induced HCC EMT and elucidate the molecular mechanisms in vitro. Our results showed that EGF promoted EMT in HCC cell lines as evidenced by altered morphology, expression of EMT-associated markers, and enhanced invasion capacity. Furthermore, the present study also revealed that nuclear translocation of PKM2, which is regulated by ERK pathway, regulated β-catenin-TCF/LEF-1 transcriptional activity and associated EMT in HCC cell lines. These discoveries provide evidence of novel roles of PKM2 in the progression of HCC and potential therapeutic target for advanced cases.
Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China; E-mail : profyinlu@163.com.
Fang-Tian
FT
Fan
Cun-Si
CS
Shen
Li
L
Tao
Chao
C
Tian
Zhao-Guo
ZG
Liu
Zhi-Jie
ZJ
Zhu
Yu-Ping
YP
Liu
Chang-Song
CS
Pei
Hong-Yan
HY
Wu
Lei
L
Zhang
Ai-Yun
AY
Wang
Shi-Zhong
SZ
Zheng
Shi-Le
SL
Huang
Yin
Y
Lu
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D004815:Epidermal Growth Factor / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D011379:Prognosis; D051820:TCF Transcription Factors / Q000235:genetics; D013963:Thyroid Hormones / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics; D051176:beta Catenin / Q000235:genetics; D000097810:Thyroid Hormone-Binding Proteins
D002352:Carrier Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D051821:Lymphoid Enhancer-Binding Factor 1; D008565:Membrane Proteins; D051820:TCF Transcription Factors; D013963:Thyroid Hormones; D051176:beta Catenin; D000097810:Thyroid Hormone-Binding Proteins; C497573:LEF1 protein, human; C512478:EGFR protein, human