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

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.

Functions of the multi‐interacting protein KIDINS220/ARMS in cancer and other pathologies

“…It's downregulation also decreased the tumorigenicity in severe combined immunodeficient mice, strongly evidencing the functional role of the protein in this disease . This was validated in another study by the same authors, together with the finding of a correlation between KIDINS220 protein expression and clinical outcome for melanoma patients . Indeed, there was a better overall survival of patients with a negative KIDINS220 expression as compared to those with weak, moderate, or strong expression.…”

Ph‐like acute lymphoblastic leukemia with a novel PAX5‐KIDINS220 fusion transcript

“…Interestingly, KIDINS220 expression levels are associated with outcome in melanoma patients. Thus, KIDINS220 is important roles in cancer progression and is a potential therapeutic target (Liao et al, 2007(Liao et al, , 2011.…”

Kidins220/ARMS as a functional mediator of multiple receptor signalling pathways

“…Indeed, Trk receptors were originally identified as oncogenes (Martin-Zanca et al, 1986). It is therefore not surprising that Kidins220/ARMS was suggested to have a role as an oncogene and that it is overexpressed in melanoma, a skin cancer of neural crest origin (Liao et al, 2007;Liao et al 2011) and possibly in other types of cancer. Understanding how to control the activity of Kidins220/ARMS during tumour progression, for example by specifically targeting its NTPase domain, represents a possible avenue for therapeutic intervention and an attractive means to study the balance between death and survival signals.…”

“…Accordingly, Kidins220/ARMS prevents stressinduced apoptosis in melanoma cells and contributes to tumour progression (Liao et al, 2007;Liao et al, 2011).…”