title: Pyruvate kinase M2 facilitates colon cancer cell migration via the modulation of STAT3 signalling.
abstract: Understanding the mechanisms of colorectal cancer (CRC) metastatic progression is essential to reducing its morbidity and mortality. Pyruvate kinase (PK) catalyses the final step of glycolysis and has been identified as a critical regulator of glucose consumption. However, the mechanisms and roles of PKM1 and PKM2 in the regulation of CRC cell migration and cell adhesion remain elusive. Here, we report that PKM2 rather than PKM1 drives CRC cell migration and cell adhesion, whereas PKM attenuation reverses these phenomena. Furthermore, the overexpression of PKM2 significantly increases the expression of N-cadherin, MMP-2, MMP-9, STAT3, Snail-2, pFAK and active β1-integrin, while E-cadherin expression is suppressed. More importantly, the results indicated that PKM2 overexpression facilitates STAT3 nuclear translocation, and it is required for PKM2 function in the regulation of migration and adhesion associated signalling. In addition, the dimeric form of PKM2, which lacks the pyruvate kinase activities but possesses protein kinase activity, is critical for CRC cell migration and cell adhesion. Overall, this study suggests that PKM2 overexpression promotes CRC cell migration and cell adhesion by regulating STAT3-associated signalling and that PKM2 may serve as a therapeutic target for CRC metastasis.
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China. Electronic address: peng114011@163.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
authors.forename: Zongwei
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Fu
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
authors.forename: Haili
authors.initials: H
authors.lastname: Wu
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China; College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China. Electronic address: lzy@sxu.edu.cn.
authors.forename: Zhuoyu
authors.initials: Z
authors.lastname: Li
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology; D019281:Dimerization; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D011770:Pyruvate Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D019012:Integrin beta1; D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C000604407:SNAI1 protein, human; D050796:STAT3 Transcription Factor; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D011770:Pyruvate Kinase; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Adhesion; Colorectal cancer; Migration; PKM1; PKM2