title: PGRMC1 Elevation in Multiple Cancers and Essential Role in Stem Cell Survival.
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 cytoch-romeb5related 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.
authors.affiliation: Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
authors.forename: Kaia K
authors.initials: KK
authors.lastname: Hampton
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, KY, USA; Markey Cancer Center, University of Kentucky, Lexington, KY, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Stewart
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, KY, USA; Markey Cancer Center, University of Kentucky, Lexington, KY, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Napier
authors.affiliation: Department of Biomolecular Sciences and National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS, USA; Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Claudio
authors.affiliation: Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA; Markey Cancer Center, University of Kentucky, Lexington, KY, USA.
authors.forename: Rolf J
authors.initials: RJ
authors.lastname: Craven
keywords: Head and Neck Cancer; Lung Cancer; Oral Cancer; PGRMC1; Stem Cells