Abstract：
Gastrointestinal tumors are the most common tumors, and they are leading cause of cancer deaths worldwide, but their mechanisms are still unclear, which need to be clarified to discover therapeutic targets. p21-activating kinase (PAK), a serine/threonine kinase that is downstream of Rho GTPase, plays an important role in cellular signaling networks. According to the structural characteristics and activation mechanisms of them, PAKs are divided into two groups, both of which are involved in the biological processes that are critical to cells, including proliferation, migration, survival, transformation and metabolism. The biological functions of PAKs depend on a large number of interacting proteins and the signaling pathways they participate in. The role of PAKs in tumors is manifested in their abnormality and the consequential changes in the signaling pathways. Once they are overexpressed or overactivated, PAKs lead to tumorigenesis or a malignant phenotype, especially in tumor invasion and metastasis. Recently, the involvement of PAKs in cellular plasticity, stemness and the tumor microenvironment have attracted attention. Here, we summarize the biological characteristics and key signaling pathways of PAKs, and further analyze their mechanisms in gastrointestinal tumors and others, which will reveal new therapeutic targets and a theoretical basis for the clinical treatment of gastrointestinal cancer.
摘要：
胃肠道肿瘤是最常见的肿瘤，它们是全球癌症死亡的主要原因，但是它们的机制仍然不清楚，需要澄清以发现治疗靶标。p21激活激酶（PAK），RhoGTP酶下游的丝氨酸/苏氨酸激酶，在蜂窝信令网络中起着重要的作用。根据其结构特点和活化机理,PAK分为两组，两者都参与了对细胞至关重要的生物过程，包括扩散，迁移,生存,转化和新陈代谢。PAK的生物学功能取决于大量相互作用的蛋白质及其参与的信号通路。PAK在肿瘤中的作用表现为其异常和信号通路的相应变化。一旦它们过度表达或过度激活，PAK导致肿瘤发生或恶性表型，尤其是在肿瘤的侵袭和转移中。最近,PAK参与细胞可塑性，干细胞和肿瘤微环境引起了人们的关注。这里,我们总结了PAKs的生物学特性和关键信号通路，并进一步分析它们在胃肠道肿瘤和其他肿瘤中的作用机制，新的治疗靶点,为临床治疗消化道肿瘤提供理论依据。
