ABSTRACT
Monocarboxylate transporter 1 (MCT1) inhibition is thought to block tumor growth through disruption of lactate transport and glycolysis. Here, we show MCT1 inhibition impairs proliferation of glycolytic breast cancer cells co-expressing MCT1 and MCT4 via disruption of pyruvate rather than lactate export. MCT1 expression is elevated in glycolytic breast tumors, and high MCT1 expression predicts poor prognosis in breast and lung cancer patients. Acute MCT1 inhibition reduces pyruvate export but does not consistently alter lactate transport or glycolytic flux in breast cancer cells that co-express MCT1 and MCT4. Despite the lack of glycolysis impairment, MCT1 loss-of-function decreases breast cancer cell proliferation and blocks growth of mammary fat pad xenograft tumors. Our data suggest MCT1 expression is elevated in glycolytic cancers to promote pyruvate export that when inhibited, enhances oxidative metabolism and reduces proliferation. This study presents an alternative molecular consequence of MCT1 inhibitors, further supporting their use as anti-cancer therapeutics.
Subject(s)
Breast Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Monocarboxylic Acid Transporters/genetics , Muscle Proteins/genetics , Pyruvic Acid/metabolism , Symporters/genetics , Animals , Antineoplastic Agents/pharmacology , Biological Transport , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Citric Acid Cycle/drug effects , Citric Acid Cycle/genetics , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Epithelial Cells/pathology , Female , Gene Expression Profiling , Glycolysis/drug effects , Glycolysis/genetics , Humans , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Mice , Monocarboxylic Acid Transporters/antagonists & inhibitors , Monocarboxylic Acid Transporters/metabolism , Muscle Proteins/metabolism , Oxidative Phosphorylation/drug effects , Pyrimidinones/pharmacology , Signal Transduction , Symporters/antagonists & inhibitors , Symporters/metabolism , Thiophenes/pharmacology , Tumor Burden/drug effects , Xenograft Model Antitumor AssaysABSTRACT
In many cultures, the erect penis has been a symbol of masculine qualities. Because of this symbolism, a penis that is less than average size can cause insecurity or embarrassment. This series reports the authors' 18-year experience in the management of 60 men with a complaint of a small penis. For 44 of these 60 men, counseling was sufficient; the other 16 had surgery, and of these, 9 were satisfied with the result. Despite limitations, the authors conclude that those men who already achieve a penis length of no less than 7.5 cm (2.95 in) in erection, have only limited benefit from penis-enhancing surgery. This particular patient category should therefore be dissuaded from surgery.
Subject(s)
Patient Satisfaction , Penile Diseases/therapy , Penile Erection , Penis/anatomy & histology , Adolescent , Adult , Body Image , Counseling , Humans , Male , Middle Aged , Self Concept , Young AdultABSTRACT
Penis lengthening pills, stretch apparatus, vacuum pumps, silicone injections, and lengthening and thickening operations are available for men who worry about their penis size. Surgery is thus far the only proven scientific method for penile enlargement. In this article, we consider patient selection, outcome evaluation, and techniques applied. In our view, sexological counseling and detailed explanation of risks and complications are mandatory before any operative intervention.
