title: STAP-2 Protein Expression in B16F10 Melanoma Cells Positively Regulates Protein Levels of Tyrosinase, Which Determines Organs to Infiltrate in the Body.
abstract: Melanoma is the most serious type of skin cancer, with a highly metastatic phenotype. In this report, we show that signal transducing adaptor protein 2 (STAP-2) is involved in cell migration, proliferation, and melanogenesis as well as chemokine receptor expression and tumorigenesis in B16F10 melanoma cells. This was evident in mice injected with STAP-2 shRNA (shSTAP-2)-expressing B16F10 cells, which infiltrated organs in a completely different pattern from the original cells, showing massive colonization in the liver, kidney, and neck but not in the lung. The most important finding was that STAP-2 expression determined tyrosinase protein content. STAP-2 colocalized with tyrosinase in lysosomes and protected tyrosinase from protein degradation. It is noteworthy that B16F10 cells with knocked down tyrosinase showed similar cell characteristics as shSTAP-2 cells. These results indicated that tyrosinase contributed to some cellular events beyond melanogenesis. Taken together, one possibility is that STAP-2 positively regulates the protein levels of tyrosinase, which determines tumor invasion via controlling chemokine receptor expression.
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sekine
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812, Japan.
authors.forename: Sumihito
authors.initials: S
authors.lastname: Togi
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Muromoto
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kon
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kitai
authors.affiliation: the Department of Microbiology and Immunology, Keio University School of Medicine, Shinjuku-Ku, Tokyo 160-8582, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
authors.affiliation: the Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Oritani
authors.affiliation: From the Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-Ku, Sapporo, 060-0812, Japan, tmatsuda@pharm.hokudai.ac.jp.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D048430:Cell Shape; D002470:Cell Survival; D055785:Gene Knockdown Techniques; D008247:Lysosomes / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D008546:Melanoma, Experimental / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008543:Melanins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; C523144:STAP2 protein, mouse; D014442:Monophenol Monooxygenase
keywords: adaptor protein; chemokine; melanoma; protein degradation; tumor metastasis; tyrosinase