Recent investigations indicate that β2-adrenergic receptor (β2-AR) signaling may facilitate the progression of various tumors, whose underlying mechanisms remain largely elusive. In the present study, we showed that β2-AR recruited Cdc42 in response to isoproterenol (ISO, a β-AR selective agonist) exposure in pancreatic ductal adenocarcinoma (PDAC) cells. The association of β2-AR and Cdc42 promoted the activation of Cdc42, as revealed by increased levels of Cdc42-GTP, and co-incubation with β2-AR antagonist abrogated ISO-induced activation of Cdc42. β2-AR-mediated Cdc42 activation further led to the phosphorylation of downstream PAK1, LIMK1 and Merlin. Furthermore, we showed that the activation of β2-AR/Cdc42 signaling facilitated the migration and invasion of PDAC cells. In addition, β2-AR and Cdc42 were overexpressed in PDAC specimens, compared with adjacent non-tumor tissues. High expression of β2-AR and Cdc42 were correlated with lymph node metastasis and TNM stage in PDAC patients. Finally, we showed that overexpression of β2-AR and Cdc42 were indicative of unfavorable prognosis in PDAC patients. Taken together, our findings suggested that β2-AR might facilitate Cdc42 signaling to drive the migration and invasion of PDAC cells, consequently resulting in the metastasis and dismal prognosis of PDAC. These studies highlight targeting β2-AR/Cdc42 signaling as a therapeutic strategy against PDAC.

最近的研究表明，β2-肾上腺素能受体 (β2-AR) 信号传导可能促进各种肿瘤的进展，其潜在机制在很大程度上仍然难以捉摸。在本研究中，我们发现 β2-AR 募集 Cdc42 以响应胰腺导管腺癌细胞 (PDAC) 中的异丙肾上腺素（ISO，一种 β-AR 选择性激动剂）暴露。β2-AR 和 Cdc42 的结合促进了 Cdc42 的活化，正如 Cdc42-GTP 水平升高所揭示的那样，并且与 β2-AR 拮抗剂的共同孵育消除了 ISO 诱导的 Cdc42 活化。β2-AR 介导的 Cdc42 激活进一步导致下游 PAK1、LIMK1 和 Merlin 的磷酸化。此外，我们发现 β2-AR/Cdc42 信号通路的激活促进了 PDAC 细胞的迁移和侵袭。此外，β2-AR 和 Cdc42 在 PDAC 标本中过表达，与邻近的非肿瘤组织相比。β2-AR 和 Cdc42 的高表达与 PDAC 患者的淋巴结转移和 TNM 分期相关。最后，我们发现 β2-AR 和 Cdc42 的过表达表明 PDAC 患者预后不良。总之，我们的研究结果表明，β2-AR 可能促进 Cdc42 信号传导以驱动 PDAC 细胞的迁移和侵袭，从而导致 PDAC 的转移和不良预后。这些研究强调了靶向 β2-AR/Cdc42 信号作为针对 PDAC 的治疗策略。我们的研究结果表明，β2-AR 可能促进 Cdc42 信号传导以驱动 PDAC 细胞的迁移和侵袭，从而导致 PDAC 的转移和预后不良。这些研究强调了靶向 β2-AR/Cdc42 信号作为针对 PDAC 的治疗策略。我们的研究结果表明，β2-AR 可能促进 Cdc42 信号传导以驱动 PDAC 细胞的迁移和侵袭，从而导致 PDAC 的转移和预后不良。这些研究强调了靶向 β2-AR/Cdc42 信号作为针对 PDAC 的治疗策略。