Upregulated ankyrin repeat-rich membrane spanning protein contributes to tumour progression in cutaneous melanoma.

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.