Journal of Cellular Biochemistry

Cover image for Vol. 116 Issue 6

Edited By: C. Fred Fox, Gary S. Stein, and Max M. Burger

Impact Factor: 3.368

ISI Journal Citation Reports © Ranking: 2013: 90/185 (Cell Biology); 107/291 (Biochemistry & Molecular Biology)

Online ISSN: 1097-4644

Recently Published Issues

See all

Top Cited Articles 2014

Gillies, L. A. and Kuwana, T.
Apoptosis Regulation at the Mitochondrial Outer Membrane
Journal of Cellular Biochemistry 2014, vol. 115, p. 632

Song, L., Li, Y., Li, W., Wu, S. and Li, Z.
miR-495 Enhances the Sensitivity of Non-Small Cell Lung Cancer Cells to Platinum by Modulation of Copper-Transporting P-type Adenosine Triphosphatase A (ATP7A)
Journal of Cellular Biochemistry 2014, vol. 115, p. 1234

Shang, J., Yang, F., Wang, Y., Wang, Y., Xue, G., Mei, Q., Wang, F. and Sun, S..
MicroRNA-23a Antisense Enhances 5-Fluorouracil Chemosensitivity Through APAF-1/Caspase-9 Apoptotic Pathway in Colorectal Cancer Cells
Journal of Cellular Biochemistry 2014, vol. 115, p. 772

Tsimbouri, P., Gadegaard, N., Burgess, K., White, K., Reynolds, P., Herzyk, P., Oreffo, R. and Dalby, M. J
Nanotopographical Effects on Mesenchymal Stem Cell Morphology and Phenotype
Journal of Cellular Biochemistry 2014, vol. 115, p. 380

Cai, Y., Cai, T. and Chen, Y.
Wnt Pathway in Osteosarcoma, from Oncogenic to Therapeutic
Journal of Cellular Biochemistry 2014, vol. 115, p. 625

See More Here

SEO Tips for Authors

SEO Author

JCB Spotlight Article

The RUNX2 Transcription Factor Negatively Regulates SIRT6 Expression to Alter Glucose Metabolism in Breast Cancer Cells

Moran Choe, Jessica L. Brusgard, Sara Chumsri, Lekhana Bhandary, X. Frank Zhao, Song Lu, Olga G. Goloubeva, Brian M. Polster, Gary M. Fiskum, Geoffrey D. Girnun, Myoung Sook Kim, and Antonino Passaniti

Activation of genes promoting aerobic glycolysis and suppression of mitochondrial oxidative phosphorylation is one of the hallmarks of cancer. The RUNX2 transcription factor mediates breast cancer (BC) metastasis to bone and is regulated by glucose availability. But, the mechanisms by which it regulates glucose metabolism and promotes an oncogenic phenotype are not known. RUNX2 expression in luminal BC cells correlated with lower estrogen receptor-α (ERα) levels, anchorage-independent growth, expression of glycolytic genes, increased glucose uptake, and sensitivity to glucose starvation, but not to inhibitors of oxidative phosphorylation. Conversely, RUNX2 knockdown in triple-negative BC cells inhibited mammosphere formation and glucose dependence. RUNX2 knockdown resulted in lower LDHA, HK2, and GLUT1 glycolytic gene expression, but upregulation of pyruvate dehydrogenase-A1 (PDHA1) mRNA and enzymatic activity, which was consistent with lower glycolytic potential. The NAD-dependent histone deacetylase, SIRT6, a known tumor suppressor, was a critical regulator of these RUNX2-mediated metabolic changes. RUNX2 expression resulted in elevated pAkt, HK2, and PDHK1 glycolytic protein levels that were reduced by ectopic expression of SIRT6. RUNX2 also repressed mitochondrial oxygen consumption rates (OCR), a measure of oxidative phosphorylation (respiration). Overexpression of SIRT6 increased respiration in RUNX2-positive cells, but knockdown of SIRT6 in cells expressing low RUNX2 decreased respiration. RUNX2 repressed SIRT6 expression at both the transcriptional and post-translational levels and endogenous SIRT6 expression was lower in malignant BC tissues or cell lines that expressed high levels of RUNX2. These results support a hypothesis whereby RUNX2-mediated repression of the SIRT6 tumor suppressor regulates metabolic pathways that promote BC progression.



BIOCHEMISTRY EcThis content will be freely available to all through September 17th. Don't miss out.

New Content

Subscribe to RSS headline updates from: Journal of Cellular Biochemistry
Powered by FeedBurner