Arginine deprivation is currently being evaluated for its efficacy and safety in clinical trials aimed at combating tumors. However, the cellular signaling and molecular changes in response to such deprivation have not been systematically deciphered. Here, we evaluate the effect of arginine deprivation on human pancreatic cancer cells, with respect to their migratory and invasive potentials and their ability to undergo epithelial-mesenchymal transition (EMT). The transcription factors Snail, Slug, and Twist are regulators of EMT, as indicated by the suppression of E-cadherin and other epithelial markers and adhesion molecules. Our data indicated that arginine starvation inhibited the migration and impaired the adhesion and invasion of the pancreatic cancer cells, decreased Snail, Slug, and Twist expression, and increased E-cadherin expression without altering the expression of vimentin. It is well known that matrix metalloproteinases (MMPs) are important for the events that underlie tumor dissemination. Arginine starvation inhibited the expression of MMP-1 and MMP-9. Furthermore, the PI3K/Akt pathway was altered when the pancreatic cancer cells underwent arginine deprivation as exhibited by the decreased Akt phosphorylation. Thus, these data reveal that arginine deprivation has the potential to decrease the metastatic ability of pancreatic cancer cells.

中文翻译：

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精氨酸剥夺通过下调Snail，Slug，Twist和MMP1 / 9抑制胰腺癌细胞的迁移，侵袭和EMT

目前，在针对肿瘤的临床试验中正在评估精氨酸剥夺的功效和安全性。但是，尚未系统地解密响应于这种剥夺的细胞信号传导和分子变化。在这里，我们评估精氨酸剥夺对人类胰腺癌细胞的影响，涉及其迁移和侵袭潜能以及它们经历上皮-间质转化（EMT）的能力。转录因子Snail，Slug和Twist是EMT的调节剂，如抑制E-钙粘蛋白和其他上皮标记物和粘附分子所表明的。我们的数据表明，精氨酸饥饿会抑制胰腺癌细胞的迁移并损害其粘附和侵袭，Snail，Slug和Twist表达降低，并增加E-钙粘蛋白的表达，而不会改变波形蛋白的表达。众所周知，基质金属蛋白酶（MMPs）对于肿瘤扩散的基础很重要。精氨酸饥饿抑制了MMP-1和MMP-9的表达。此外，当胰腺癌细胞经历精氨酸剥夺时，PI3K / Akt途径也发生了改变，如Akt磷酸化水平降低所显示的。因此，这些数据表明精氨酸剥夺具有降低胰腺癌细胞转移能力的潜力。当胰腺癌细胞经历精氨酸剥夺时，PI3K / Akt途径发生改变，这是由Akt磷酸化水平降低所显示的。因此，这些数据表明精氨酸剥夺具有降低胰腺癌细胞转移能力的潜力。当胰腺癌细胞经历精氨酸剥夺时，PI3K / Akt途径发生改变，这是由Akt磷酸化水平降低所显示的。因此，这些数据表明精氨酸剥夺具有降低胰腺癌细胞转移能力的潜力。