title: Testes-specific protease 50 promotes cell invasion and metastasis by increasing NF-kappaB-dependent matrix metalloproteinase-9 expression.
abstract: The high mortality in breast cancer is often associated with metastatic progression in patients. Previously we have demonstrated that testes-specific protease 50 (TSP50), an oncogene overexpressed in breast cancer samples, could promote cell proliferation and tumorigenesis. However, whether TSP50 also has a key role in cell invasion and cancer metastasis, and the mechanism underlying the process are still unclear. Here we found that TSP50 overexpression greatly promoted cell migration, invasion, adhesion and formation of the stellate structures in 3D culture system in vitro as well as lung metastasis in vivo. Conversely, TSP50 knockdown caused the opposite changes. Mechanistic studies revealed that NF-κB signaling pathway was required for TSP50-induced cell migration and metastasis, and further results indicated that TSP50 overexpression enhanced expression and secretion of MMP9, a target gene of NF-κB signaling. In addition, knockdown of MMP9 resulted in inhibition of cell migration and invasion in vitro and lung metastasis in vivo. Most importantly, immunohistochemical staining of human breast cancer samples strongly showed that the coexpression of TSP50 and p65 as well as TSP50 and MMP9 were correlated with increased metastasis and poor survival. Furthermore, we found that some breast cancer diagnosis-associated features such as tumor size, tumor grade, estrogen receptors (ER) and progesterone receptors (PR) levels, were correlated well with TSP50/p65 and TSP50/MMP9 expression status. Taken together, this work identified the TSP50 activation of MMP9 as a novel signaling mechanism underlying human breast cancer invasion and metastasis.
authors: 1] National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China [2] Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun 130024, China.
authors: Z B
authors: ZB
authors: Song
authors: Department of Pathology, the First Hospital of Jilin University, Changchun 130041, China.
authors: J-S
authors: JS
authors: Ni
authors: Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun 130024, China.
authors: P
authors: P
authors: Wu
authors: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China.
authors: Y L
authors: YL
authors: Bao
authors: Department of Pathology, the First Hospital of Jilin University, Changchun 130041, China.
authors: T
authors: T
authors: Liu
authors: Department of Pathology, the First Hospital of Jilin University, Changchun 130041, China.
authors: M
authors: M
authors: Li
authors: Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
authors: C
authors: C
authors: Fan
authors: 1] National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China [2] Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun 130024, China.
authors: W J
authors: WJ
authors: Zhang
authors: 1] National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China [2] Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun 130024, China.
authors: L G
authors: LG
authors: Sun
authors: 1] Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun 130024, China [2] Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
authors: Y X
authors: YX
authors: Huang
authors: 1] Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun 130024, China [2] Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
authors: Y X
authors: YX
authors: Li
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000378:metabolism; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D016019:Survival Analysis; D013737:Testis / Q000378:metabolism; D051996:Transcription Factor RelA / Q000096:biosynthesis* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D016328:NF-kappa B; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D051996:Transcription Factor RelA; D012697:Serine Endopeptidases; C446379:testis-specific protease 50; D020780:Matrix Metalloproteinase 9