Upregulated ankyrin repeat-rich membrane spanning protein contributes to tumour progression in cutaneous melanoma
Journal
British Journal of Cancer
Journal Volume
104
Journal Issue
6
Pages
982-988
Date Issued
2011
Author(s)
Abstract
Background:We have previously demonstrated that overexpression of ankyrin repeat-rich membrane spanning (ARMS) protein facilitates melanoma formation via conferring apoptotic resistance. This study aims to investigate whether ARMS contributes to melanoma progression.Method:Using immunohistochemistry, we graded the expression level of ARMS in 54 cases of primary melanoma and 46 cases of metastatic melanoma. The immunointensity of ARMS was statistically correlated with individual clinicopathological characteristics. By RNA interference, stable melanoma cell clones with ARMS-knockdown were constructed, and were used for in vitro scratch wound, transwell invasion assays, and in vivo lung metastasis experiment.Results:Stronger immunointensity of ARMS was observed mostly in melanomas with Breslow tumour thickness 1.0 mm (Fisher's exact test, P=0.002) or with nodal metastasis (Fisher's exact test, P=0.026), and was correlated with a worse overall survival in melanoma patients (log-rank test, P=0.04). Depletion of ARMS inhibited migration, invasion, and metastatic potential of melanoma cells in vitro and in vivo. Moreover, ARMS mediated melanoma cell migration and invasion through activation of the extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signalling pathway.Conclusion:Ankyrin repeat-rich membrane spanning expression, conjunctly with tumour thickness or ulceration, may serve as a prognostic factor in patients with cutaneous melanoma. ? 2011 Cancer Research UK All rights reserved.
SDGs
Other Subjects
ankyrin repeat rich membrane spanning protein; membrane protein; mitogen activated protein kinase; mitogen activated protein kinase kinase; unclassified drug; adult; animal cell; animal experiment; animal model; animal tissue; article; cancer invasion; cell migration; controlled study; enzyme activation; female; human; human cell; human tissue; in vitro study; in vivo study; lung metastasis; lymph node metastasis; major clinical study; male; melanoma; melanoma cell; metastasis potential; mouse; nonhuman; nucleotide sequence; priority journal; prognosis; protein expression; signal transduction; skin melanoma; tumor growth; upregulation; Adult; Aged; Aged, 80 and over; Animals; Disease Progression; Female; Humans; Immunohistochemistry; Male; Melanoma; Membrane Proteins; Mice; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Nerve Tissue Proteins; Prognosis; Skin Neoplasms; Survival Analysis; Tumor Markers, Biological; Up-Regulation
Type
journal article