CancerCell.org

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Cancer Cell Online

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The cover shows an MRI image of a double mutant mouse (bottom middle) generated by the crossing of a HMGA2 transgenic mouse (upper right) with an E2F1 null mouse (upper left). Lack of the E2F1 transcription factor prevents the onset of pituitary adenomas, which develop in HMGA2 transgenic mice (indicated in circle). Thus, HMGA2-mediated E2F1 activation is a crucial event in the development of these tumors. For details, see the article by Fedele et al. (pp. 459 –471 ).

Alterations in cellular metabolism are among the most consistent hallmarks of cancer. Herein we have investigated the relationship between increased aerobic lactate production and mitochondrial physiology in tumor cells. To diminish the ability of malignant cells to metabolize pyruvate to lactate, lactate dehydrogenase A (LDH-A) levels were knocked down by means of LDH-A short hairpin RNAs. Reduction in LDH-A activity resulted in stimulation of mitochondrial respiration and decrease of mitochondrial membrane potential. It also compromised the ability of these tumor cells to proliferate under hypoxia. The tumorigenicity of the LDH-A-deficient cells was severely diminished, and this phenotype was reversed by complementation with the human ortholog LDH-A protein. These results demonstrate that LDH-A plays a key role in tumor maintenance.

These are the Top 20 Papers by download from the Cancer Cell web site for the last 30 days. You can see the summaries if you are registered, or full text and PDFs if you have subscribed.