Secreted pyruvate kinase M2 facilitates cell migration via PI3K/Akt and Wnt/β-catenin pathway in colon cancer cells

Extensive studies have been reported the non-canonical functions of pyruvate kinase M2 (PKM2) as a kinase, transcriptional regulator, and even cell-to-cell communicator, emphasizing its importance in various signaling pathways. However, the role of secreted PKM2 in cancer progression and its signaling pathway is yet to be elucidated. In this study, we found that extracellular PKM2 enhanced the migration of low-metastatic, benign colon cancer cells by upregulating claudin-1 expression and internalizing it to the cytoplasm and nucleus. Knock-down of claudin-1 significantly reduced extracellular PKM2-induced cell migration. Inhibition of either protein kinase C (PKC) or epidermal growth factor receptor (EGFR) resulted in a reduction of extracellular PKM2-mediated claudin-1 expression, suggesting EGFR–PKC–claudin-1 as a signaling pathway in the extracellular PKM2-mediated tumorigenesis of colon cancer cells.

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A role of zinc-finger protein 143 for cancer cell migration and invasion through ZEB1 and E-cadherin in colon cancer cells

Molecular Carcinogenesis ◽

10.1002/mc.22083 ◽

2013 ◽

Vol 53 (S1) ◽

pp. E161-E168 ◽

Cited By ~ 18

Author(s):

A Rome Paek ◽

Chang-Hoon Lee ◽

Hye Jin You

Keyword(s):

Colon Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Zinc Finger ◽

Zinc Finger Protein ◽

Migration And Invasion ◽

Cancer Cell Migration ◽

Colon Cancer Cells ◽

Finger Protein

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Atypical role of sprouty in colorectal cancer: sprouty repression inhibits epithelial–mesenchymal transition

Oncogene ◽

10.1038/onc.2015.365 ◽

2015 ◽

Vol 35 (24) ◽

pp. 3151-3162 ◽

Cited By ~ 16

Author(s):

Q Zhang ◽

T Wei ◽

K Shim ◽

K Wright ◽

K Xu ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Migration And Invasion ◽

Colon Cancer Cells ◽

Mesenchymal Transition ◽

E Cadherin

Abstract Sprouty (SPRY) appears to act as a tumor suppressor in cancer, whereas we demonstrated that SPRY2 functions as a putative oncogene in colorectal cancer (CRC) (Oncogene, 2010, 29: 5241–5253). We investigated the mechanisms by which SPRY regulates epithelial–mesenchymal transition (EMT) in CRC. SPRY1 and SPRY2 mRNA transcripts were significantly upregulated in human CRC. Suppression of SPRY2 repressed AKT2 and EMT-inducing transcription factors and significantly increased E-cadherin expression. Concurrent downregulation of SPRY1 and SPRY2 also increased E-cadherin and suppressed mesenchymal markers in colon cancer cells. An inverse expression pattern between AKT2 and E-cadherin was established in a human CRC tissue microarray. SPRY2 negatively regulated miR-194-5p that interacts with AKT2 3′ untranslated region. Mir-194 mimics increased E-cadherin expression and suppressed cancer cell migration and invasion. By confocal microscopy, we demonstrated redistribution of E-cadherin to plasma membrane in colon cancer cells transfected with miR-194. Spry1 −/− and Spry2 −/− double mutant mouse embryonic fibroblasts exhibited decreased cell migration while acquiring several epithelial markers. In CRC, SPRY drive EMT and may serve as a biomarker of poor prognosis.

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Different functions of AKT1 and AKT2 in molecular pathways, cell migration and metabolism in colon cancer cells

International Journal of Oncology ◽

10.3892/ijo.2016.3771 ◽

2016 ◽

Vol 50 (1) ◽

pp. 5-14 ◽

Cited By ~ 25

Author(s):

Sara Häggblad Sahlberg ◽

Anja C. Mortensen ◽

Jakob Haglöf ◽

Mikael K.R. Engskog ◽

Torbjörn Arvidsson ◽

...

Keyword(s):

Colon Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Molecular Pathways ◽

Colon Cancer Cells

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nm23-H1 reducesin vitro cell migration and the liver metastatic potential of colon cancer cells by regulating myosin light chain phosphorylation

International Journal of Cancer ◽

10.1002/ijc.11546 ◽

2003 ◽

Vol 108 (2) ◽

pp. 207-211 ◽

Cited By ~ 62

Author(s):

Eiji Suzuki ◽

Tetsuya Ota ◽

Kazunori Tsukuda ◽

Atsushi Okita ◽

Kinya Matsuoka ◽

...

Keyword(s):

Colon Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Light Chain ◽

Myosin Light Chain ◽

Metastatic Potential ◽

Myosin Light Chain Phosphorylation ◽

Colon Cancer Cells

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SRSF3, a Splicer of the PKM Gene, Regulates Cell Growth and Maintenance of Cancer-Specific Energy Metabolism in Colon Cancer Cells

International Journal of Molecular Sciences ◽

10.3390/ijms19103012 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3012 ◽

Cited By ~ 22

Author(s):

Yuki Kuranaga ◽

Nobuhiko Sugito ◽

Haruka Shinohara ◽

Takuya Tsujino ◽

Kohei Taniguchi ◽

...

Keyword(s):

Colon Cancer ◽

Energy Metabolism ◽

Cancer Cells ◽

Pyruvate Kinase ◽

Specific Energy ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Positive Role ◽

Polypyrimidine Tract Binding Protein

Serine and arginine rich splicing factor 3 (SRSF3), an SR-rich family protein, has an oncogenic function in various kinds of cancer. However, the detailed mechanism of the function had not been previously clarified. Here, we showed that the SRSF3 splicer regulated the expression profile of the pyruvate kinase, which is one of the rate-limiting enzymes in glycolysis. Most cancer cells express pyruvate kinase muscle 2 (PKM2) dominantly to maintain a glycolysis-dominant energy metabolism. Overexpression of SRSF3, as well as that of another splicer, polypyrimidine tract binding protein 1 (PTBP1) and heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), in clinical cancer samples supported the notion that these proteins decreased the Pyruvate kinase muscle 1 (PKM1)/PKM2 ratio, which positively contributed to a glycolysis-dominant metabolism. The silencing of SRSF3 in human colon cancer cells induced a marked growth inhibition in both in vitro and in vivo experiments and caused an increase in the PKM1/PKM2 ratio, thus resulting in a metabolic shift from glycolysis to oxidative phosphorylation. At the same time, the silenced cells were induced to undergo autophagy. SRSF3 contributed to PKM mRNA splicing by co-operating with PTBP1 and hnRNPA1, which was validated by the results of RNP immunoprecipitation (RIP) and immunoprecipitation (IP) experiments. These findings altogether indicated that SRSF3 as a PKM splicer played a positive role in cancer-specific energy metabolism.

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