Koul Hari K, Pal Mantu, Koul Sweaty
Department of Biochemistry & Molecular Biology, LSU Health Sciences Center, Shreveport, LA, USA ; Feist-Weiller Cancer Center, Shreveport, LA, USA ; Veterans Administration Medical Center, Shreveport, LA, USA.
Department of Biochemistry & Molecular Biology, LSU Health Sciences Center, Shreveport, LA, USA ; Veterans Administration Medical Center, Shreveport, LA, USA.
Genes Cancer. 2013 Sep;4(9-10):342-59. doi: 10.1177/1947601913507951.
Mitogen-activated protein kinases (MAPKs) mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the main subgroups, the p38 MAP kinases, has been implicated in a wide range of complex biologic processes, such as cell proliferation, cell differentiation, cell death, cell migration, and invasion. Dysregulation of p38 MAPK levels in patients are associated with advanced stages and short survival in cancer patients (e.g., prostate, breast, bladder, liver, and lung cancer). p38 MAPK plays a dual role as a regulator of cell death, and it can either mediate cell survival or cell death depending not only on the type of stimulus but also in a cell type specific manner. In addition to modulating cell survival, an essential role of p38 MAPK in modulation of cell migration and invasion offers a distinct opportunity to target this pathway with respect to tumor metastasis. The specific function of p38 MAPK appears to depend not only on the cell type but also on the stimuli and/or the isoform that is activated. p38 MAPK signaling pathway is activated in response to diverse stimuli and mediates its function by components downstream of p38. Extrapolation of the knowledge gained from laboratory findings is essential to address the clinical significance of p38 MAPK signaling pathways. The goal of this review is to provide an overview on recent progress made in defining the functions of p38 MAPK pathways with respect to solid tumor biology and generate testable hypothesis with respect to the role of p38 MAPK as an attractive target for intervention of solid tumors.
丝裂原活化蛋白激酶（MAPKs）介导细胞对细胞外刺激做出的多种细胞行为。主要亚组之一，即p38 MAP激酶，参与了广泛的复杂生物学过程，如细胞增殖、细胞分化、细胞死亡、细胞迁移和侵袭。癌症患者（如前列腺癌、乳腺癌、膀胱癌、肝癌和肺癌）中p38 MAPK水平失调与疾病晚期和生存期短相关。p38 MAPK作为细胞死亡的调节因子发挥双重作用，它不仅可以根据刺激类型，还可以以细胞类型特异性方式介导细胞存活或细胞死亡。除了调节细胞存活外，p38 MAPK在调节细胞迁移和侵袭方面的重要作用为针对肿瘤转移靶向该信号通路提供了独特的机会。p38 MAPK的具体功能似乎不仅取决于细胞类型，还取决于刺激和/或被激活的亚型。p38 MAPK信号通路在对多种刺激的反应中被激活，并通过p38下游的组分介导其功能。从实验室研究结果中推断出的知识对于阐明p38 MAPK信号通路的临床意义至关重要。本综述的目的是概述在确定p38 MAPK通路在实体瘤生物学中的功能方面取得的最新进展，并就p38 MAPK作为实体瘤干预的有吸引力靶点的作用提出可验证的假设。
