Kallikrein-Related Peptidase 6 (KLK6) as a Contributor toward an Aggressive Cancer Cell Phenotype: A Potential Role in Colon Cancer Peritoneal Metastasis
Kallikrein-related peptidases (KLKs) are implicated in many cancer-related processes. KLK6, one of the 15 KLK family members, is a promising biomarker for diagnosis of many cancers and has been associated with poor prognosis of colorectal cancer (CRC) patients. Herein, we evaluated the expression an...
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MDPI AG
2022-07-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/7/1003 |
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| author | Hayet Bouzid Feryel Soualmia Katerina Oikonomopoulou Antoninus Soosaipillai Francine Walker Khaoula Louati Rea Lo Dico Marc Pocard Chahrazade El Amri Natalia A. Ignatenko Dalila Darmoul |
| author_facet | Hayet Bouzid Feryel Soualmia Katerina Oikonomopoulou Antoninus Soosaipillai Francine Walker Khaoula Louati Rea Lo Dico Marc Pocard Chahrazade El Amri Natalia A. Ignatenko Dalila Darmoul |
| author_sort | Hayet Bouzid |
| collection | DOAJ |
| description | Kallikrein-related peptidases (KLKs) are implicated in many cancer-related processes. KLK6, one of the 15 KLK family members, is a promising biomarker for diagnosis of many cancers and has been associated with poor prognosis of colorectal cancer (CRC) patients. Herein, we evaluated the expression and cellular functions of KLK6 in colon cancer-derived cell lines and in clinical samples from CRC patients. We showed that, although many KLKs transcripts are upregulated in colon cancer-derived cell lines, KLK6, KLK10, and KLK11 are the most highly secreted proteins. KLK6 induced calcium flux in HT29 cells by activation and internalization of protease-activated receptor 2 (PAR2). Furthermore, KLK6 induced extracellular signal–regulated kinases 1 and 2 (ERK1/2) phosphorylation. KLK6 suppression in HCT-116 colon cancer cells decreased the colony formation, increased cell adhesion to extracellular matrix proteins, and reduced spheroid formation and compaction. Immunohistochemistry (IHC) analysis demonstrated ectopic expression of KLK6 in human colon adenocarcinomas but not in normal epithelia. Importantly, high levels of KLK6 protein were detected in the ascites of CRC patients with peritoneal metastasis, but not in benign ascites. These data indicate that KLK6 overexpression is associated with aggressive CRC, and may be applied to differentiate between benign and malignant ascites. |
| first_indexed | 2024-03-09T12:10:13Z |
| format | Article |
| id | doaj.art-022da2a0d5b54c6ab2da745c01190ed5 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T12:10:13Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-022da2a0d5b54c6ab2da745c01190ed52023-11-30T22:52:42ZengMDPI AGBiomolecules2218-273X2022-07-01127100310.3390/biom12071003Kallikrein-Related Peptidase 6 (KLK6) as a Contributor toward an Aggressive Cancer Cell Phenotype: A Potential Role in Colon Cancer Peritoneal MetastasisHayet Bouzid0Feryel Soualmia1Katerina Oikonomopoulou2Antoninus Soosaipillai3Francine Walker4Khaoula Louati5Rea Lo Dico6Marc Pocard7Chahrazade El Amri8Natalia A. Ignatenko9Dalila Darmoul10Institut National de la Santé et de la Recherche Médicale (INSERM) INSERM-1275, Hôpital Lariboisière, 75010 Paris, FranceSorbonne Université, IBPS, UMR 8256 CNRS-UPMC, ERL INSERM U1164, Biological Adaptation and Ageing, 75005 Paris, FranceSchroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto, ON M5T 3L9, CanadaDepartment of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON M5T 3L9, CanadaDepartment of Pathology, Hôpital Bichat-Claude Bernard, 75018 Paris, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM) INSERM-1275, Hôpital Lariboisière, 75010 Paris, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM) INSERM-1275, Hôpital Lariboisière, 75010 Paris, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM) INSERM-1275, Hôpital Lariboisière, 75010 Paris, FranceSorbonne Université, IBPS, UMR 8256 CNRS-UPMC, ERL INSERM U1164, Biological Adaptation and Ageing, 75005 Paris, FranceUniversity of Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USAInstitut National de la Santé et de la Recherche Médicale (INSERM) INSERM-1275, Hôpital Lariboisière, 75010 Paris, FranceKallikrein-related peptidases (KLKs) are implicated in many cancer-related processes. KLK6, one of the 15 KLK family members, is a promising biomarker for diagnosis of many cancers and has been associated with poor prognosis of colorectal cancer (CRC) patients. Herein, we evaluated the expression and cellular functions of KLK6 in colon cancer-derived cell lines and in clinical samples from CRC patients. We showed that, although many KLKs transcripts are upregulated in colon cancer-derived cell lines, KLK6, KLK10, and KLK11 are the most highly secreted proteins. KLK6 induced calcium flux in HT29 cells by activation and internalization of protease-activated receptor 2 (PAR2). Furthermore, KLK6 induced extracellular signal–regulated kinases 1 and 2 (ERK1/2) phosphorylation. KLK6 suppression in HCT-116 colon cancer cells decreased the colony formation, increased cell adhesion to extracellular matrix proteins, and reduced spheroid formation and compaction. Immunohistochemistry (IHC) analysis demonstrated ectopic expression of KLK6 in human colon adenocarcinomas but not in normal epithelia. Importantly, high levels of KLK6 protein were detected in the ascites of CRC patients with peritoneal metastasis, but not in benign ascites. These data indicate that KLK6 overexpression is associated with aggressive CRC, and may be applied to differentiate between benign and malignant ascites.https://www.mdpi.com/2218-273X/12/7/1003kallikrein-related peptidase 6protease-activated receptorscolorectal cancermetastasissignalingextracellular matrix |
| spellingShingle | Hayet Bouzid Feryel Soualmia Katerina Oikonomopoulou Antoninus Soosaipillai Francine Walker Khaoula Louati Rea Lo Dico Marc Pocard Chahrazade El Amri Natalia A. Ignatenko Dalila Darmoul Kallikrein-Related Peptidase 6 (KLK6) as a Contributor toward an Aggressive Cancer Cell Phenotype: A Potential Role in Colon Cancer Peritoneal Metastasis Biomolecules kallikrein-related peptidase 6 protease-activated receptors colorectal cancer metastasis signaling extracellular matrix |
| title | Kallikrein-Related Peptidase 6 (KLK6) as a Contributor toward an Aggressive Cancer Cell Phenotype: A Potential Role in Colon Cancer Peritoneal Metastasis |
| title_full | Kallikrein-Related Peptidase 6 (KLK6) as a Contributor toward an Aggressive Cancer Cell Phenotype: A Potential Role in Colon Cancer Peritoneal Metastasis |
| title_fullStr | Kallikrein-Related Peptidase 6 (KLK6) as a Contributor toward an Aggressive Cancer Cell Phenotype: A Potential Role in Colon Cancer Peritoneal Metastasis |
| title_full_unstemmed | Kallikrein-Related Peptidase 6 (KLK6) as a Contributor toward an Aggressive Cancer Cell Phenotype: A Potential Role in Colon Cancer Peritoneal Metastasis |
| title_short | Kallikrein-Related Peptidase 6 (KLK6) as a Contributor toward an Aggressive Cancer Cell Phenotype: A Potential Role in Colon Cancer Peritoneal Metastasis |
| title_sort | kallikrein related peptidase 6 klk6 as a contributor toward an aggressive cancer cell phenotype a potential role in colon cancer peritoneal metastasis |
| topic | kallikrein-related peptidase 6 protease-activated receptors colorectal cancer metastasis signaling extracellular matrix |
| url | https://www.mdpi.com/2218-273X/12/7/1003 |
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