title: Pyruvate kinase M2 plays a dual role on regulation of the EGF/EGFR signaling via E-cadherin-dependent manner in gastric cancer cells.
abstract: OBJECTIVE
  EGFR activation and PKM2 expression are instrumental in tumorigenesis. EGFR activation regulates PKM2 functions in a subcellular compartment-dependent manner and promotes gene transcription and tumor growth. In addition, PKM2 is upregulated in EGFR-induced pathways in glioma malignancies. However, we found that PKM2 could also regulate the activity of the EGF/EGFR signaling pathway in gastric cancer cells. We aimed to define the biological mechanisms for PKM2 in regulating the cell motility and invasion.
  
  
  METHODS
  We employed stable transfection with short hairpin RNA to stably silence the expression of PKM2 in the BGC823, SGC7901 and AGS gastric cancer cell lines. The effects of PKM2 in vitro were determined by assessing cell migration and invasion. Immunohistochemical analysis was used to explore the relationship among PKM2 and other proteins.
  
  
  RESULTS
  Our results indicate that the knockdown of PKM2 decreased the activity of E-cadherin and enhanced the EGF/EGFR signaling pathway in the gastric cell lines BGC823 and SGC7901 that were positive for E-cadherin expression. However, in the undifferentiated gastric carcinoma cell line AGS, which lacks E-cadherin expression, PKM2 promoted cell migration and invasion. Immunohistochemical analyses showed that the levels of E-cadherin expression, ERK1/2 phosphorylation, and cytoplasmic PKM2 expression were correlated with each other.
  
  
  CONCLUSIONS
  PKM2 may play different roles in differently differentiated gastric cancer cell types, and this finding would be consistent with the previous clinical research. The results of our study reveal an important link between PKM2 and E-cadherin during EGFR-stimulated gastric cancer cell motility and invasion.
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital affiliated to Xiamen University, Xiamen, Fujian Province, China.
authors.forename: Le-Yi
authors.initials: LY
authors.lastname: Wang
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Liu
authors.forename: Li-Gang
authors.initials: LG
authors.lastname: Chen
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Tan
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Liu
authors.forename: Amarsanaa
authors.initials: A
authors.lastname: Jazag
authors.forename: Jian-Lin
authors.initials: JL
authors.lastname: Ren
authors.forename: Bayasi
authors.initials: B
authors.lastname: Guleng
mesh_terms: D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D004815:Epidermal Growth Factor / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013963:Thyroid Hormones / Q000235:genetics* / Q000378:metabolism; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D015820:Cadherins; D002352:Carrier Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D008565:Membrane Proteins; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins; C512478:EGFR protein, human