TITLE:
PGRMC1 Elevation in Multiple Cancers and Essential Role in Stem Cell Survival
AUTHORS:
Kaia K. Hampton, Rachel Stewart, Dana Napier, Pier Paolo Claudio, Rolf J. Craven
KEYWORDS:
Lung Cancer, Oral Cancer, Head and Neck Cancer, Stem Cells, PGRMC1
JOURNAL NAME:
Advances in Lung Cancer,
Vol.4 No.3,
January
28,
2016
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.