Emerging significance of ER-coregulator PELP1/MNAR in cancer.
The estrogen receptors ERalpha and ERbeta have been implicated in the progression of a wide variety of cancers. The actions of ER are regulated by ER coregulator proteins, including proline-, glutamic acid- and leucine-rich-protein-1 (PELP1/MNAR). PELP1 has been shown to participate in both genomic and nongenomic functions of ER. The expression and localization of PELP1/MNAR are deregulated in a wide variety of tumors and have been implicated in the development of hormonal resistance in cancer cell lines. Emerging data suggest that PELP1/MNAR interacts with many proteins and activates several oncogenes, including Src kinase, phosphotidyl inositol 3 kinase (PI3K), and signal transducers and activators of transcription 3 (STAT3). These new results suggest that PELP1/MNAR may act as an oncogene as well as cooperating with other oncogenes. Thus, PELP1/MNAR may contribute to the tumorigenic potential of cancer cells by serving as a scaffolding protein that couples various signaling complexes with ER.
Nair
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Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, Texas, USA.
Vadlamudi
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D056970:Co-Repressor Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors
D056970:Co-Repressor Proteins; C438485:PELP1 protein, human; D011960:Receptors, Estrogen; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D019869:Phosphatidylinositol 3-Kinases