A tumor suppressor function for the lipid phosphatase INPP4B in melanocytic neoplasms

Rolando Perez-Lorenzo; Kamraan Z Gill; Che-Hung Shen; Feng X Zhao; Bin Zheng; Hans-Joachim Schulze; David N Silvers; Georg Brunner; Basil A Horst

doi:10.1038/jid.2013.511

A tumor suppressor function for the lipid phosphatase INPP4B in melanocytic neoplasms

J Invest Dermatol. 2014 May;134(5):1359-1368. doi: 10.1038/jid.2013.511. Epub 2013 Nov 28.

Authors

Rolando Perez-Lorenzo¹, Kamraan Z Gill², Che-Hung Shen³, Feng X Zhao¹, Bin Zheng³, Hans-Joachim Schulze⁴, David N Silvers¹, Georg Brunner⁵, Basil A Horst⁶

Affiliations

¹ Department of Dermatology, Columbia University Medical Center, New York, New York, USA.
² Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA.
³ Institute for Cancer Genetics, Columbia University, New York, New York, USA.
⁴ Department of Dermatology, Fachklinik Hornheide at University Muenster, Muenster, Germany.
⁵ Department of Cancer Research, Fachklinik Hornheide at University Muenster, Muenster, Germany.
⁶ Department of Dermatology, Columbia University Medical Center, New York, New York, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA. Electronic address: bh2179@cumc.columbia.edu.

PMID: 24288008
DOI: 10.1038/jid.2013.511

Abstract

The phosphoinositide-3 kinase (PI3K) pathway is deregulated in a significant proportion of melanomas, and PI3K pathway activation in combination with constitutively active mitogen-activated protein kinase signaling shows synergistic effects in the process of melanoma tumorigenesis. Recently, a tumor suppressor function for the lipid phosphatase inositol polyphosphate 4-phosphatase type II (INPP4B) has been described in breast and prostate cancers, with impact on PI3K signaling output. Given the importance of PI3K pathway activity for melanoma formation and growth, we aimed to assess the role of INPP4B in melanocytic tumors. Our studies in native tumors suggest that decreased INPP4B expression is an event correlating with tumor progression in melanocytic neoplasms. We further demonstrate that INPP4B regulates PI3K/Akt signaling and exerts a tumor suppressor effect, impacting the proliferative, invasive, and tumorigenic capacity of melanoma cells. INPP4B expression in melanocytic neoplasms may therefore have potential as a biomarker for disease progression and as a modulator for the prediction of treatment outcome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / enzymology
Adenocarcinoma / genetics
Adenocarcinoma / pathology
Animals
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
Breast Neoplasms / enzymology
Breast Neoplasms / genetics
Breast Neoplasms / pathology
Cell Line, Transformed
Cell Line, Tumor
Cell Movement / physiology
Female
GTP Phosphohydrolases / genetics
Genes, Tumor Suppressor / physiology
Humans
MCF-7 Cells
Melanoma / enzymology*
Melanoma / genetics
Melanoma / pathology
Membrane Proteins / genetics
Mice
Mice, Nude
Neoplasm Invasiveness
Neoplasm Transplantation
Phosphatidylinositol 3-Kinases / metabolism*
Phosphoric Monoester Hydrolases / genetics*
Phosphoric Monoester Hydrolases / metabolism*
Proto-Oncogene Proteins B-raf / genetics
Proto-Oncogene Proteins c-akt / metabolism
Skin Neoplasms / enzymology*
Skin Neoplasms / genetics
Skin Neoplasms / pathology
Tissue Banks

Substances

Biomarkers, Tumor
Membrane Proteins
Phosphatidylinositol 3-Kinases
AKT1 protein, human
BRAF protein, human
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins c-akt
Phosphoric Monoester Hydrolases
phosphatidylinositol-3,4-bisphosphate 4-phosphatase
GTP Phosphohydrolases
NRAS protein, human