Knocking down claudin receptors leads to a decrease in prostate cancer cell migration, cell growth, cell viability and clonogenic cell survival
Abstract Prostate cancer is the most common solid organ malignancy in the United States, and has the highest probability of all cancers in becoming invasive. New molecular targets are needed to define and impede the growth and progression of advanced prostate cancers. Claudins (Cldns) are transmembr...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Springer
2021-10-01
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| Series: | Molecular Biomedicine |
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| Online Access: | https://doi.org/10.1186/s43556-021-00053-0 |
| _version_ | 1818908773415124992 |
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| author | Qiang Liu Hongliang Shen Andrew Naguib Robert M. Weiss Darryl T. Martin |
| author_facet | Qiang Liu Hongliang Shen Andrew Naguib Robert M. Weiss Darryl T. Martin |
| author_sort | Qiang Liu |
| collection | DOAJ |
| description | Abstract Prostate cancer is the most common solid organ malignancy in the United States, and has the highest probability of all cancers in becoming invasive. New molecular targets are needed to define and impede the growth and progression of advanced prostate cancers. Claudins (Cldns) are transmembrane proteins that regulate paracellular permeability and cell polarity, and their levels are elevated in many human cancers such as breast, ovarian, pancreatic, and prostatic cancers. Previously, we found that Cldn3 and Cldn4 are expressed in aggressive high-grade human prostate cancer specimens. We and others have shown that there are higher levels of Cldn3 and Cldn4 in metastatic human prostate cancer cells than in normal human prostate cells. The result of targeting Cldn3 and Cldn4 expression on the growth and viability of prostate cancer cells has not been elucidated. Human prostate cancer PC3 and LNCaP cells were transfected with Cldn3 or -4 small interfering RNAs (siRNAs). Cldn3/Cldn4 siRNA treatment resulted in a greater than 85% decrease in the protein levels of Cldn3 and Cldn4, which was accompanied by a 30–40% decrease in prostate cancer cell growth and a 60–65% reduction in cell viability. There was decreased cell migration with Cldn3 and Cldn4 siRNA in both PC3 and LNCaP cells and a 60–75% decrease in the number of clones when treated with siCldn3 or siCldn4 compared to control. Knocking down Cldn3/Cldn4 affects prostate cancer cell growth and survival and may have therapeutic implications. |
| first_indexed | 2024-12-19T22:16:21Z |
| format | Article |
| id | doaj.art-c624955bc4414a9d99ea71b8f4f5f5b5 |
| institution | Directory Open Access Journal |
| issn | 2662-8651 |
| language | English |
| last_indexed | 2024-12-19T22:16:21Z |
| publishDate | 2021-10-01 |
| publisher | Springer |
| record_format | Article |
| series | Molecular Biomedicine |
| spelling | doaj.art-c624955bc4414a9d99ea71b8f4f5f5b52022-12-21T20:03:46ZengSpringerMolecular Biomedicine2662-86512021-10-01211910.1186/s43556-021-00053-0Knocking down claudin receptors leads to a decrease in prostate cancer cell migration, cell growth, cell viability and clonogenic cell survivalQiang Liu0Hongliang Shen1Andrew Naguib2Robert M. Weiss3Darryl T. Martin4Department of Urology, Yale University School of MedicineDepartment of Urology, Yale University School of MedicineDepartment of Urology, Yale University School of MedicineDepartment of Urology, Yale University School of MedicineDepartment of Urology, Yale University School of MedicineAbstract Prostate cancer is the most common solid organ malignancy in the United States, and has the highest probability of all cancers in becoming invasive. New molecular targets are needed to define and impede the growth and progression of advanced prostate cancers. Claudins (Cldns) are transmembrane proteins that regulate paracellular permeability and cell polarity, and their levels are elevated in many human cancers such as breast, ovarian, pancreatic, and prostatic cancers. Previously, we found that Cldn3 and Cldn4 are expressed in aggressive high-grade human prostate cancer specimens. We and others have shown that there are higher levels of Cldn3 and Cldn4 in metastatic human prostate cancer cells than in normal human prostate cells. The result of targeting Cldn3 and Cldn4 expression on the growth and viability of prostate cancer cells has not been elucidated. Human prostate cancer PC3 and LNCaP cells were transfected with Cldn3 or -4 small interfering RNAs (siRNAs). Cldn3/Cldn4 siRNA treatment resulted in a greater than 85% decrease in the protein levels of Cldn3 and Cldn4, which was accompanied by a 30–40% decrease in prostate cancer cell growth and a 60–65% reduction in cell viability. There was decreased cell migration with Cldn3 and Cldn4 siRNA in both PC3 and LNCaP cells and a 60–75% decrease in the number of clones when treated with siCldn3 or siCldn4 compared to control. Knocking down Cldn3/Cldn4 affects prostate cancer cell growth and survival and may have therapeutic implications.https://doi.org/10.1186/s43556-021-00053-0Cell receptorsMolecular targeted therapyCancer cell survivalCancer cell migrationClaudin-3 (Cldn3)Claudin-4 (Cldn4) |
| spellingShingle | Qiang Liu Hongliang Shen Andrew Naguib Robert M. Weiss Darryl T. Martin Knocking down claudin receptors leads to a decrease in prostate cancer cell migration, cell growth, cell viability and clonogenic cell survival Molecular Biomedicine Cell receptors Molecular targeted therapy Cancer cell survival Cancer cell migration Claudin-3 (Cldn3) Claudin-4 (Cldn4) |
| title | Knocking down claudin receptors leads to a decrease in prostate cancer cell migration, cell growth, cell viability and clonogenic cell survival |
| title_full | Knocking down claudin receptors leads to a decrease in prostate cancer cell migration, cell growth, cell viability and clonogenic cell survival |
| title_fullStr | Knocking down claudin receptors leads to a decrease in prostate cancer cell migration, cell growth, cell viability and clonogenic cell survival |
| title_full_unstemmed | Knocking down claudin receptors leads to a decrease in prostate cancer cell migration, cell growth, cell viability and clonogenic cell survival |
| title_short | Knocking down claudin receptors leads to a decrease in prostate cancer cell migration, cell growth, cell viability and clonogenic cell survival |
| title_sort | knocking down claudin receptors leads to a decrease in prostate cancer cell migration cell growth cell viability and clonogenic cell survival |
| topic | Cell receptors Molecular targeted therapy Cancer cell survival Cancer cell migration Claudin-3 (Cldn3) Claudin-4 (Cldn4) |
| url | https://doi.org/10.1186/s43556-021-00053-0 |
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