Cystatin M/E (Cystatin 6): A Janus-Faced Cysteine Protease Inhibitor with Both Tumor-Suppressing and Tumor-Promoting Functions
Alongside its contribution in maintaining skin homeostasis and its probable involvement in fetal and placental development, cystatin M/E (also known as cystatin 6) was first described as a tumor suppressor of breast cancer. This review aims to provide an update on cystatin M/E with particular attent...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/8/1877 |
| _version_ | 1797537748047888384 |
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| author | Gilles Lalmanach Mariana Kasabova-Arjomand Fabien Lecaille Ahlame Saidi |
| author_facet | Gilles Lalmanach Mariana Kasabova-Arjomand Fabien Lecaille Ahlame Saidi |
| author_sort | Gilles Lalmanach |
| collection | DOAJ |
| description | Alongside its contribution in maintaining skin homeostasis and its probable involvement in fetal and placental development, cystatin M/E (also known as cystatin 6) was first described as a tumor suppressor of breast cancer. This review aims to provide an update on cystatin M/E with particular attention paid to its role during tumorigenesis. Cystatin M/E, which is related to type 2 cystatins, displays the unique property of being a dual tight-binding inhibitor of both legumain (also known as asparagine endopeptidase) and cysteine cathepsins L, V and B, while its expression level is epigenetically regulated via the methylation of the <i>CST6</i> promoter region. The tumor-suppressing role of cystatin M/E was further reported in melanoma, cervical, brain, prostate, gastric and renal cancers, and cystatin M/E was proposed as a biomarker of prognostic significance. Contrariwise, cystatin M/E could have an antagonistic function, acting as a tumor promoter (e.g., oral, pancreatic cancer, thyroid and hepatocellular carcinoma). Taking into account these apparently divergent functions, there is an urgent need to decipher the molecular and cellular regulatory mechanisms of the expression and activity of cystatin M/E associated with the safeguarding homeostasis of the proteolytic balance as well as its imbalance in cancer. |
| first_indexed | 2024-03-10T12:20:37Z |
| format | Article |
| id | doaj.art-d22f621d65f54aebb4d18c4a90b4e653 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T12:20:37Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-d22f621d65f54aebb4d18c4a90b4e6532023-11-21T15:33:38ZengMDPI AGCancers2072-66942021-04-01138187710.3390/cancers13081877Cystatin M/E (Cystatin 6): A Janus-Faced Cysteine Protease Inhibitor with Both Tumor-Suppressing and Tumor-Promoting FunctionsGilles Lalmanach0Mariana Kasabova-Arjomand1Fabien Lecaille2Ahlame Saidi3Faculté de Médecine, Université de Tours, 37000 Tours, FranceCovance CAPS Ltd., 1404 Sofia, BulgariaFaculté de Médecine, Université de Tours, 37000 Tours, FranceFaculté de Médecine, Université de Tours, 37000 Tours, FranceAlongside its contribution in maintaining skin homeostasis and its probable involvement in fetal and placental development, cystatin M/E (also known as cystatin 6) was first described as a tumor suppressor of breast cancer. This review aims to provide an update on cystatin M/E with particular attention paid to its role during tumorigenesis. Cystatin M/E, which is related to type 2 cystatins, displays the unique property of being a dual tight-binding inhibitor of both legumain (also known as asparagine endopeptidase) and cysteine cathepsins L, V and B, while its expression level is epigenetically regulated via the methylation of the <i>CST6</i> promoter region. The tumor-suppressing role of cystatin M/E was further reported in melanoma, cervical, brain, prostate, gastric and renal cancers, and cystatin M/E was proposed as a biomarker of prognostic significance. Contrariwise, cystatin M/E could have an antagonistic function, acting as a tumor promoter (e.g., oral, pancreatic cancer, thyroid and hepatocellular carcinoma). Taking into account these apparently divergent functions, there is an urgent need to decipher the molecular and cellular regulatory mechanisms of the expression and activity of cystatin M/E associated with the safeguarding homeostasis of the proteolytic balance as well as its imbalance in cancer.https://www.mdpi.com/2072-6694/13/8/1877biomarkerbreast cancercathepsincystatincysteine proteaselegumain |
| spellingShingle | Gilles Lalmanach Mariana Kasabova-Arjomand Fabien Lecaille Ahlame Saidi Cystatin M/E (Cystatin 6): A Janus-Faced Cysteine Protease Inhibitor with Both Tumor-Suppressing and Tumor-Promoting Functions Cancers biomarker breast cancer cathepsin cystatin cysteine protease legumain |
| title | Cystatin M/E (Cystatin 6): A Janus-Faced Cysteine Protease Inhibitor with Both Tumor-Suppressing and Tumor-Promoting Functions |
| title_full | Cystatin M/E (Cystatin 6): A Janus-Faced Cysteine Protease Inhibitor with Both Tumor-Suppressing and Tumor-Promoting Functions |
| title_fullStr | Cystatin M/E (Cystatin 6): A Janus-Faced Cysteine Protease Inhibitor with Both Tumor-Suppressing and Tumor-Promoting Functions |
| title_full_unstemmed | Cystatin M/E (Cystatin 6): A Janus-Faced Cysteine Protease Inhibitor with Both Tumor-Suppressing and Tumor-Promoting Functions |
| title_short | Cystatin M/E (Cystatin 6): A Janus-Faced Cysteine Protease Inhibitor with Both Tumor-Suppressing and Tumor-Promoting Functions |
| title_sort | cystatin m e cystatin 6 a janus faced cysteine protease inhibitor with both tumor suppressing and tumor promoting functions |
| topic | biomarker breast cancer cathepsin cystatin cysteine protease legumain |
| url | https://www.mdpi.com/2072-6694/13/8/1877 |
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