title: CAPC negatively regulates NF-κB activation and suppresses tumor growth and metastasis.
abstract: CAPC, also known as LRRC26, is expressed in normal prostate and salivary gland. We developed a mAb to CAPC and used it to characterize the protein and study its function. CAPC protein was detected in normal prostate and salivary gland, in several human breast cancer cell lines and in the prostate cancer cell line LNCaP. Knockdown of CAPC by siRNA in LNCaP cells enhanced anchorage-independent growth in soft agar. Conversely, overexpression of CAPC in MDA-231 breast cancer cells and A431 epidermoid cancer cells inhibited growth in soft agar and tumorigenesis in nude mice, and suppressed the metastasis of MDA-231 cells to the lung. Overexpression of CAPC downregulated NF-κB activity and its target genes, including GM-CSF (CSF2), CXCL1, IL8 and LTB1. It also suppressed genes encoding the serine protease mesotrypsin (PRSS3) and cystatin SN (CST1). CAPC expressing tumors showed a decrease in the number of proliferating cells and a large increase in ECM. The role of CAPC in the suppression of tumor growth and metastasis may be through its alteration of the tumor microenvironment.
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264, USA.
authors.forename: X-F
authors.initials: XF
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Xiang
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: K G
authors.initials: KG
authors.lastname: Becker
authors.forename: T K
authors.initials: TK
authors.lastname: Bera
authors.forename: I
authors.initials: I
authors.lastname: Pastan
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000235:genetics; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: C539913:LRRC26 protein, human; D016328:NF-kappa B; D009363:Neoplasm Proteins