title: Aberrant Expression of proPTPRN2 in Cancer Cells Confers Resistance to Apoptosis.
abstract: The protein tyrosine phosphatase receptor PTPRN2 is expressed predominantly in endocrine and neuronal cells, where it functions in exocytosis. We found that its immature isoform proPTPRN2 is overexpressed in various cancers, including breast cancer. High proPTPRN2 expression was associated strongly with lymph node-positive breast cancer and poor clinical outcome. Loss of proPTPRN2 in breast cancer cells promoted apoptosis and blocked tumor formation in mice, whereas enforced expression of proPTPRN2 in nontransformed human mammary epithelial cells exerted a converse effect. Mechanistic investigations suggested that ProPTPRN2 elicited these effects through direct interaction with TRAF2, a hub scaffold protein for multiple kinase cascades, including ones that activate NF-κB. Overall, our results suggest PTPRN2 as a novel candidate biomarker and therapeutic target in breast cancer.
authors: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Alexey V
authors: AV
authors: Sorokin
authors: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Binoj C
authors: BC
authors: Nair
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Yongkun
authors: Y
authors: Wei
authors: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Kathryn E
authors: KE
authors: Aziz
authors: Department of Genomics, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
authors: Valentina
authors: V
authors: Evdokimova
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan.
authors: Mien-Chie
authors: MC
authors: Hung
authors: Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. jchen8@mdanderson.org.
authors: Junjie
authors: J
authors: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D064593:Heterografts; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D061986:MCF-7 Cells; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
chemical_list: D016328:NF-kappa B; C102889:PTPRN2 protein, human; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8