Piastra Valentina, Pranteda Angelina, Bossi Gianluca
Oncogenomic and Epigenetic Unit, Department of Diagnostic Research and Technological Innovation, IRCC-Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
Cancers (Basel). 2022 Jan 18;14(3):483. doi: 10.3390/cancers14030483.
The role played by MKK3 in human cancer is controversial. MKK3 is an evolutionarily conserved protein kinase that activates in response to a variety of stimuli. Phosphorylates, specifically the p38MAPK family proteins, contribute to the regulation of a plethora of cellular processes such as proliferation, differentiation, apoptosis, invasion, and cell migration. Genes in carcinogenesis are classified as oncogenes and tumor suppressors; however, a clear distinction is not always easily made as it depends on the cell context and tissue specificity. The aim of this study is the examination of the potential contribution of MKK3 in cancer through a systematic analysis of the recent literature. The overall results reveal a complex scenario of MKK3's involvement in cancer. The oncogenic functions of MKK3 were univocally documented in several solid tumors, such as colorectal, prostate cancer, and melanoma, while its tumor-suppressing functions were described in glioblastoma and gastric cancer. Furthermore, a dual role of MKK3 as an oncogene as well as tumor a suppressor has been described in breast, cervical, ovarian, liver, esophageal, and lung cancer. However, overall, more evidence points to its role as an oncogene in these diseases. This review indicates that the oncogenic and tumor-suppressing roles of MKK3 are strictly dependent on the tumor type and further suggests that MKK3 could represent an efficient putative molecular target that requires contextualization within a specific tumor type in order to adequately evaluate its potential effectiveness in designing novel anticancer therapies.
MKK3在人类癌症中所起的作用存在争议。MKK3是一种进化上保守的蛋白激酶，可响应多种刺激而激活。磷酸化，特别是p38MAPK家族蛋白的磷酸化，有助于调节大量细胞过程，如增殖、分化、凋亡、侵袭和细胞迁移。致癌过程中的基因分为癌基因和肿瘤抑制基因；然而，由于取决于细胞背景和组织特异性，并非总是能轻易明确区分。本研究的目的是通过对近期文献的系统分析来考察MKK3在癌症中的潜在作用。总体结果揭示了MKK3参与癌症的复杂情况。MKK3的致癌功能在几种实体瘤中得到明确记载，如结直肠癌、前列腺癌和黑色素瘤，而其肿瘤抑制功能则在胶质母细胞瘤和胃癌中有所描述。此外，MKK3在乳腺癌、宫颈癌、卵巢癌、肝癌、食管癌和肺癌中被描述为具有癌基因和肿瘤抑制基因的双重作用。然而，总体而言，更多证据表明其在这些疾病中作为癌基因的作用。本综述表明，MKK3的致癌和肿瘤抑制作用严格取决于肿瘤类型，并进一步表明MKK3可能是一个有效的假定分子靶点，为了充分评估其在设计新型抗癌疗法中的潜在有效性，需要在特定肿瘤类型中进行背景分析。
