Dissection of the MKK3 Functions in Human Cancer: A Double-Edged Sword?
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 prolifer...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/3/483 |
| _version_ | 1797488865244610560 |
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| author | Valentina Piastra Angelina Pranteda Gianluca Bossi |
| author_facet | Valentina Piastra Angelina Pranteda Gianluca Bossi |
| author_sort | Valentina Piastra |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T00:09:23Z |
| format | Article |
| id | doaj.art-a7b468e70fc04ec8a524b4901276f259 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T00:09:23Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a7b468e70fc04ec8a524b4901276f2592023-11-23T16:03:34ZengMDPI AGCancers2072-66942022-01-0114348310.3390/cancers14030483Dissection of the MKK3 Functions in Human Cancer: A Double-Edged Sword?Valentina Piastra0Angelina Pranteda1Gianluca Bossi2Oncogenomic and Epigenetic Unit, Department of Diagnostic Research and Technological Innovation, IRCC—Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, ItalyOncogenomic and Epigenetic Unit, Department of Diagnostic Research and Technological Innovation, IRCC—Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, ItalyOncogenomic and Epigenetic Unit, Department of Diagnostic Research and Technological Innovation, IRCC—Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, ItalyThe 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.https://www.mdpi.com/2072-6694/14/3/483MKK3p38 MAPKoncogenetumor suppressorcancertherapeutic treatments |
| spellingShingle | Valentina Piastra Angelina Pranteda Gianluca Bossi Dissection of the MKK3 Functions in Human Cancer: A Double-Edged Sword? Cancers MKK3 p38 MAPK oncogene tumor suppressor cancer therapeutic treatments |
| title | Dissection of the MKK3 Functions in Human Cancer: A Double-Edged Sword? |
| title_full | Dissection of the MKK3 Functions in Human Cancer: A Double-Edged Sword? |
| title_fullStr | Dissection of the MKK3 Functions in Human Cancer: A Double-Edged Sword? |
| title_full_unstemmed | Dissection of the MKK3 Functions in Human Cancer: A Double-Edged Sword? |
| title_short | Dissection of the MKK3 Functions in Human Cancer: A Double-Edged Sword? |
| title_sort | dissection of the mkk3 functions in human cancer a double edged sword |
| topic | MKK3 p38 MAPK oncogene tumor suppressor cancer therapeutic treatments |
| url | https://www.mdpi.com/2072-6694/14/3/483 |
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