糖原合成酶激酶-3（glycogen synthase kinase-3,，GSK-3）是一種多功能的絲氨酸／蘇氨酸蛋白激酶,，是細胞內(nèi)多種信號轉(zhuǎn)導通路中的重要成分，不僅參與細胞內(nèi)糖代謝過程而且還參與細胞增殖,、細胞分化和細胞凋亡等多種重要生理過程。
一項最新研究主要集中于分析糖原合酶激酶（GSK）-3β信號在黑色素瘤中的作用,。免疫組化染色顯示在原位和轉(zhuǎn)移性黑色素瘤組織中GSK3β的表達分別為12和33％,。
研究發(fā)現(xiàn)GSK3抑制劑及小干擾RNA（siRNA）降低GSK3β表達能抑制黑色素細胞的運動能力，這一效應在劃痕實驗,、三維膠原蛋白植入球體以及改良Boyden小室實驗中檢測到,。
進一步探究證實抑制GSK3β信號降低N-cadherin的mRNA和蛋白表達水平，同時轉(zhuǎn)錄因子Slug的表達也下降,。抑制GSK3β信號也能抑制黑色素細胞與內(nèi)皮細胞和成纖維細胞之間的黏附，防止黑色素瘤細胞跨內(nèi)皮遷移,，而一旦恢復N-cadherin表達，上述效應被逆轉(zhuǎn),。
GSK3β信號在黑色素瘤粘附中的作用主要通過調(diào)控粘著斑激酶（FAK）的磷酸化,。總之,，GSK3β通過影響N-cadherin和FAK調(diào)節(jié)黑色素細胞的運動性和侵襲能力。這些研究表明,，抑制GSK3β是一種潛在的黑色素瘤治療方法,。（生物谷：Bioon.com）
編譯自：GSK3β Inhibition Blocks Melanoma Cell/Host Interactions by Downregulating N-Cadherin Expression and Decreasing FAK Phosphorylation
doi:10.1038/jid.2012.237
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GSK3β Inhibition Blocks Melanoma Cell/Host Interactions by Downregulating N-Cadherin Expression and Decreasing FAK Phosphorylation
Jobin K John, Kim H T Paraiso, Vito W Rebecca, Liliana P Cantini, Ethan V Abel, Nicholas Pagano, Eric Meggers, Rahel Mathew, Clemens Krepler, Victoria Izumi, Bin Fang, John M Koomen, Jane L Messina, Meenhard Herlyn and Keiran S M Smalley
This study addresses the role of glycogen synthase kinase (GSK)-3β signaling in the tumorigenic behavior of melanoma. Immunohistochemical staining revealed GSK3β to be focally expressed in the invasive portions of 12 and 33% of primary and metastatic melanomas, respectively. GSK3 inhibitors and small interfering RNA (siRNA) knockdown of GSK3β were found to inhibit the motile behavior of melanoma cells in scratch wound, three-dimensional collagen–implanted spheroid, and modified Boyden chamber assays. Functionally, inhibition of GSK3β signaling was found to suppress N-cadherin expression at the messenger RNA and protein levels, and was associated with decreased expression of the transcription factor Slug. Pharmacological and genetic ablation of GSK3β signaling inhibited the adhesion of melanoma cells to both endothelial cells and fibroblasts and prevented transendothelial migration, an effect rescued by the forced overexpression of N-cadherin. A further role for GSK3β signaling in invasion was suggested by the ability of GSK3β inhibitors and siRNA knockdown to block phosphorylation of focal adhesion kinase (FAK) and increase the size of focal adhesions. In summary, we have, to our knowledge, demonstrated a previously unreported role for GSK3β in modulating the motile and invasive behavior of melanoma cells through N-cadherin and FAK. These studies suggest the potential therapeutic utility of inhibiting GSK3β in defined subsets of melanoma.
