Data from <i>NUAK2</i> Amplification Coupled with <i>PTEN</i> Deficiency Promotes Melanoma Development via CDK Activation

• DOI: 10.1158/0008-5472.c.6506052
• Publication Date: 2024-03-12T22:57:05Z
• Authors: Takeshi Namiki; Tomonori Yaguchi; Kenta Nakamura; Julio C. Valencia; Sergio G. Coelho; Lanlan Yin; Masakazu Kawaguchi; Wilfred D. Vieira; Yasuhiko Kaneko; Atsushi Tanemura; Ichiro Katayama; Hiroo Yokozeki; Yutaka Kawakami; Vincent J. Hearing

&lt;div&gt;Abstract&lt;p&gt;The AMPK-related kinase NUAK2 has been implicated in melanoma growth and survival outcomes, but its therapeutic utility yet to be confirmed. In this study, we show how genetic amplification &lt;i&gt;PTEN&lt;/i&gt;-deficient melanomas may rationalize the use of CDK2 inhibitors as a strategy. Analysis array-CGH data revealed that &lt;i&gt;PTEN&lt;/i&gt; deficiency is coupled tightly with genomic encompassing &lt;i&gt;NUAK2&lt;/i&gt; locus, finding strengthened by immunohistochemical evidence phospho-Akt overexpression was correlated expression clinical specimens acral melanoma. Functional studies cells showed inactivation PI3K pathway upregulated p21 reduced number S phase. silencing efficiently controlled expression, whereas specifically abrogated &lt;i&gt;NUAK2&lt;/i&gt;-amplified cells. Immunohistochemical analyses confirmed an association p-Akt melanomas. Finally, pharmacologic inhibition sufficient suppress &lt;i&gt;in vitro&lt;/i&gt; vivo&lt;/i&gt;. Overall, our results blockade offer promising therapy for genetically defined melanomas, where amplified deleted. &lt;i&gt;Cancer Res; 75(13); 2708–15. ©2015 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;