AI Article Synopsis
- Pathways of metabolic changes in cancer are not fully understood; this study identifies TMPRSS11B as a key gene involved in the transformation of bronchial epithelial cells.
- TMPRSS11B is highly expressed in lung squamous cell carcinomas and its high levels correlate with poor patient survival.
- Inhibition of TMPRSS11B reduces tumor growth by affecting lactate export and metabolism, suggesting it could be a target for new cancer therapies.
Article Abstract
Pathways underlying metabolic reprogramming in cancer remain incompletely understood. We identify the transmembrane serine protease TMPRSS11B as a gene that promotes transformation of immortalized human bronchial epithelial cells (HBECs). TMPRSS11B is upregulated in human lung squamous cell carcinomas (LSCCs), and high expression is associated with poor survival of non-small cell lung cancer patients. TMPRSS11B inhibition in human LSCCs reduces transformation and tumor growth. Given that TMPRSS11B harbors an extracellular (EC) protease domain, we hypothesized that catalysis of a membrane-bound substrate modulates tumor progression. Interrogation of a set of soluble receptors revealed that TMPRSS11B promotes solubilization of Basigin, an obligate chaperone of the lactate monocarboxylate transporter MCT4. Basigin release mediated by TMPRSS11B enhances lactate export and glycolytic metabolism, thereby promoting tumorigenesis. These findings establish an oncogenic role for TMPRSS11B and provide support for the development of therapies that target this enzyme at the surface of cancer cells.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338450 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2018.10.100 | DOI Listing |
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