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PGRMC1 Elevation in Multiple Cancers and Essential Role in Stem Cell Survival

Advances in Lung Cancer 2015年第3期4卷 37-51页

作者： Kaia K. Hampton Rachel Stewart dana napier Pier Paolo Claudio Rolf J. Craven Department of Pharmacology and Nutritional Sciences University of Kentucky Lexington KY USA Department of Pathology and Laboratory Medicine University of Kentucky Lexington KY USA Markey Cancer Center University of Kentucky Lexington KY USA 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

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.

关键词： Lung Cancer Oral Cancer Head and Neck Cancer Stem Cells PGRMC1

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