Open AccessCellular localization of CIP 2A determines its prognostic impact in superficial spreading and nodular melanoma
Author(s) -
Flørenes Vivi Ann,
Emilsen Elisabeth,
Dong Hiep Phuc,
Førsund Mette,
Holm Ruth,
Slipicevic Ana
Publication year - 2015
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.425
Subject(s) - melanoma , oncogene , protein phosphatase 2 , cancer research , apoptosis , immunohistochemistry , context (archaeology) , pi3k/akt/mtor pathway , biology , cell growth , protein kinase b , cell cycle , phosphatase , phosphorylation , microbiology and biotechnology , immunology , genetics , paleontology
Abstract Cancerous inhibitor of protein phosphatase 2A ( CIP 2A) is an important oncogene contributing to cancer progression partially by regulating cMYC and AKT . We examined CIP 2A expression in cutaneous melanomas, its association with clinicopathological parameters and mapped molecular mechanisms regulated by CIP 2A in vitro. CIP 2A expression was analyzed by immunohistochemistry in 17 nevi, 132 primary melanomas and 49 metastases. Effects of si RNA ‐mediated down‐regulation on proliferation, apoptosis and signaling pathways were assessed in melanoma cell lines. In superficial spreading melanomas (SSM), high nuclear CIP 2A expression was associated with poor overall survival (OS) ( P = 0.0018). Surprisingly, high cytoplasmic expression was related to improved relapse‐free ( P = 0.031) and OS ( P = 0.014) in nodular melanomas (NM). In vitro experiments revealed that CIP2A can regulate proliferation and/or apoptosis partially through the PI3K/AKT pathway but also independently. In summary, CIP2A could represent a potential therapeutic target in SSM. However, in NM cytoplasmic CIP2A is associated with improved prognosis indicating that CIP2A has distinct, complex functions dependent on the molecular context and histological subtype. As seen in other cancer types, CIP2A can influence cMYC and AKT, but our data also suggest that in melanoma it has additional targets which need to be identified.