PGRMC1 Elevation in Multiple Cancers and Essential Role in Stem Cell Survival
Open Access
- 1 January 2015
- journal article
- research article
- Published by Scientific Research Publishing, Inc. in Advances in Lung Cancer
- Vol. 04 (03), 37-51
- https://doi.org/10.4236/alc.2015.43006
Abstract
Cancer is one of the leading causes of death in America, and there is an urgent need for new therapeutic approaches. The progesterone receptor membrane component 1 (PGRMC1) is a cytochrome b5 related protein that binds heme and is associated with signaling, apoptotic suppression and autophagy. PGRMC1 is essential for tumor formation, invasion and metastasis, and is upregulated in breast, colon, lung and thyroid tumors. In the present study, we have analyzed PGRMC1 levels in over 600 tumor sections, including a larger cohort of lung tumors than in previous studies, and report the first clinical analysis of PGRMC1 levels in human oral cavity and ovarian tumors compared to corresponding nonmalignant tissues. PGRMC1 was highly expressed in lung and ovarian cancers and correlated with patient survival. PGRMC1 has been previously associated with drug resistance, a characteristic of cancer stem cells. The stem cell theory proposes that a subset of cancerous stem cells contribute to drug resistance and tumor maintenance, and PGRMC1 was detected in lung-tumor derived stem cells. Drug treatment with a PGRMC1 inhibitor, AG-205, triggered stem cell death whereas treatment with erlotinib and the ERK inhibitor, PD98059, did not, suggesting a specific role for PGRMC1 in cancer stem cell viability. Together, our data demonstrate PGRMC1 as a potential tumor biomarker across a variety of tumors, as well as a therapeutic target for cancer stem cells.Keywords
This publication has 52 references indexed in Scilit:
- Neutrophil Gelatinase-associated Lipocalin (NGAL) Expression Is Dependent on the Tumor-associated Sigma-2 Receptor S2RPgrmc1Online Journal of Public Health Informatics, 2012
- The relationship between follicle development and progesterone receptor membrane component-1 expression in women undergoing in vitro fertilizationFertility and Sterility, 2012
- Progesterone signaling mediated through progesterone receptor membrane component-1 in ovarian cells with special emphasis on ovarian cancerSteroids, 2011
- Identification of the PGRMC1 protein complex as the putative sigma-2 receptor binding siteNature Communications, 2011
- Pgrmc1 (Progesterone Receptor Membrane Component 1) Associates with Epidermal Growth Factor Receptor and Regulates Erlotinib SensitivityOnline Journal of Public Health Informatics, 2010
- EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancerOncogene, 2010
- Progesterone inhibits apoptosis in part by PGRMC1-regulated gene expressionMolecular and Cellular Endocrinology, 2010
- PGRMC1 (progesterone receptor membrane component 1): A targetable protein with multiple functions in steroid signaling, P450 activation and drug bindingPharmacology & Therapeutics, 2009
- Autophagy in the Pathogenesis of DiseaseCell, 2008
- Measurement of the Heme Affinity for Yeast Dap1p, and Its Importance in Cellular FunctionBiochemistry, 2007