Aberrant genes promoter methylation in neural crest-derived tumors
INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS
Authors: la Torre, Annamaria; Muscarella, Lucia Anna; Parrella, Paola; Balsamo, Teresa; Bisceglia, Michele; Valori, Vanna Maria; la Torre, Antonella; Barbano, Raffaela; Perrella, Eleonora; Poeta, Maria Luana; Melchionda, Gennaro; Merla, Giuseppe; Maiello, Evaristo; Pellicano, Riccardo; Fazio, Vito Michele
Abstract
Disturbances in the epigenetic landscape by aberrant methylation of CpG islands can lead to inactivation of cancer-related genes in solid tumors. We analyzed the promoter methylation status of 6 genes previously reported as cancer-specific methylated (MCAM, SSBP2, NISCH, B4GALT1, KIF1A and RASSF1A) in 38 neural crest-derived tumors by quantitative methylation-specific real-time PCR (QMSP). The results demonstrated that the determination of the methylation status of RASSF1A is able to distinguish between normal and tumor samples in cutaneous melanomas, lung carcinoids and small bowel carcinoids. MCAM methylation levels were significantly higher in lung carcinoids tumors (p=0.001), suggesting that this alteration may represent a molecular biomarker in this tumor type.
Protein Depalmitoylation Is Induced by Wnt5a and Promotes Polarized Cell Behavior
JOURNAL OF BIOLOGICAL CHEMISTRY
Authors: Wang, Wei; Runkle, Kristin B.; Terkowski, Samantha M.; Ekaireb, Rachel I.; Witze, Eric S.
Abstract
Background: Wnt5a signaling induces asymmetric localization of the melanoma cell adhesion molecules (MCAM). Results: Wnt5a promotes MCAM depalmitoylation and point mutations in MCAM that block palmitoylation are sufficient to cause asymmetric MCAM localization. Conclusion: Wnt5a induces polarized MCAM localization by promoting MCAM depalmitoylation. Significance: These results reveal a mechanism for Wnt5a-induced polarized cell behavior. Wnt5a signaling regulates polarized cell behavior, but the downstream signaling events that promote cell polarity are not well understood. Our results show that Wnt5a promotes depalmitoylation of the melanoma cell adhesion molecule (MCAM) at cysteine 590. Mutation of Cys-590 to glycine is sufficient to polarize MCAM localization, similar to what is observed with Wnt5a stimulation. Inhibition of the depalmitoylating enzyme APT1 blocks Wnt5a-induced depalmitoylation, asymmetric MCAM localization, and cell invasion. Directly altering expression of the basal protein palmitoylation machinery is sufficient to promote cell invasion. Additionally, cancer mutations in palmitoyltransferases decrease MCAM palmitoylation and have impaired ability to suppress cell invasion. Our results provide evidence that Wnt5a induces protein depalmitoylation, which promotes polarized protein localization and cell invasion.
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