The Reduction of PSMB4 in T24 and J82 Bladder Cancer Cells Inhibits the Angiogenesis and Migration of Endothelial Cells
Bladder cancer (BC) is a malignant tumor of the urinary system with high mortality and recurrence rates. Proteasome subunit type 4 (PSMB4) is highly expressed and has been identified as having oncogenic properties in a variety of cancer types. This study aimed to explore the effect of PSMB4 knockdow...
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| Veröffentlicht in: | International journal of molecular sciences 2024-05, Vol.25 (10), p.5559 |
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| description | Bladder cancer (BC) is a malignant tumor of the urinary system with high mortality and recurrence rates. Proteasome subunit type 4 (PSMB4) is highly expressed and has been identified as having oncogenic properties in a variety of cancer types. This study aimed to explore the effect of PSMB4 knockdown on the survival, migration, and angiogenesis of human bladder cancer cells with different degrees of malignancy. We analyzed the effects of PSMB4 knockdown in bladder cancer cells and endothelial cells in the tumor microenvironment. PSMB4 was highly expressed in patients with low- and high-grade urothelial carcinoma. Inhibition of PSMB4 reduced protein expression of focal adhesion kinase (FAK) and myosin light chain (MLC), leading to reduced migration. Furthermore, the suppression of PSMB4 decreased the levels of vascular endothelial factor B (VEGF-B), resulting in lower angiogenic abilities in human bladder cancer cells. PSMB4 inhibition affected the migratory ability of HUVECs and reduced VEGFR2 expression, consequently downregulating angiogenesis. In the metastatic animal model, PSMB4 knockdown reduced the relative volumes of lung tumors. Our findings suggest the role of PSMB4 as a potential target for therapeutic strategies against human bladder cancer. |
| doi_str_mv | 10.3390/ijms25105559 |
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Proteasome subunit type 4 (PSMB4) is highly expressed and has been identified as having oncogenic properties in a variety of cancer types. This study aimed to explore the effect of PSMB4 knockdown on the survival, migration, and angiogenesis of human bladder cancer cells with different degrees of malignancy. We analyzed the effects of PSMB4 knockdown in bladder cancer cells and endothelial cells in the tumor microenvironment. PSMB4 was highly expressed in patients with low- and high-grade urothelial carcinoma. Inhibition of PSMB4 reduced protein expression of focal adhesion kinase (FAK) and myosin light chain (MLC), leading to reduced migration. Furthermore, the suppression of PSMB4 decreased the levels of vascular endothelial factor B (VEGF-B), resulting in lower angiogenic abilities in human bladder cancer cells. PSMB4 inhibition affected the migratory ability of HUVECs and reduced VEGFR2 expression, consequently downregulating angiogenesis. In the metastatic animal model, PSMB4 knockdown reduced the relative volumes of lung tumors. Our findings suggest the role of PSMB4 as a potential target for therapeutic strategies against human bladder cancer.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms25105559</identifier><identifier>PMID: 38791597</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Angiogenesis ; Animals ; Bladder cancer ; Breast cancer ; Cancer ; Cancer cells ; Cell adhesion & migration ; Cell Line, Tumor ; Cell Movement - genetics ; Cysteine Endopeptidases ; Endothelial Cells - metabolism ; Endothelial Cells - pathology ; Endothelium ; Female ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Human Umbilical Vein Endothelial Cells - metabolism ; Humans ; Hypoxia ; Lung cancer ; Male ; Metastasis ; Mice ; Neovascularization, Pathologic - genetics ; Neovascularization, Pathologic - metabolism ; Nitric oxide ; Oncology, Experimental ; Prevention ; Proteasome Endopeptidase Complex - genetics ; Proteasome Endopeptidase Complex - metabolism ; Protein expression ; Proteins ; Scientific equipment and supplies industry ; Tumor Microenvironment - genetics ; Tumors ; Urinary Bladder Neoplasms - genetics ; Urinary Bladder Neoplasms - metabolism ; Urinary Bladder Neoplasms - pathology ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor Receptor-2 - genetics ; Vascular Endothelial Growth Factor Receptor-2 - metabolism</subject><ispartof>International journal of molecular sciences, 2024-05, Vol.25 (10), p.5559</ispartof><rights>COPYRIGHT 2024 MDPI AG</rights><rights>2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c381t-c8c4aae31bb11164f9148b71641295ef10565326603266ee72bfff53eb51b213</cites><orcidid>0000-0001-6229-8189 ; 0000-0003-1085-9014 ; 0000-0001-6303-5858</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38791597$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lin, Yi-Hsuan</creatorcontrib><creatorcontrib>Chen, Tzu-Min</creatorcontrib><creatorcontrib>Tsai, Yu-Ling</creatorcontrib><creatorcontrib>Tsai, Wen-Chiuan</creatorcontrib><creatorcontrib>Wang, Hisao-Hsien</creatorcontrib><creatorcontrib>Chen, Ying</creatorcontrib><creatorcontrib>Wu, Sheng-Tang</creatorcontrib><title>The Reduction of PSMB4 in T24 and J82 Bladder Cancer Cells Inhibits the Angiogenesis and Migration of Endothelial Cells</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Bladder cancer (BC) is a malignant tumor of the urinary system with high mortality and recurrence rates. Proteasome subunit type 4 (PSMB4) is highly expressed and has been identified as having oncogenic properties in a variety of cancer types. This study aimed to explore the effect of PSMB4 knockdown on the survival, migration, and angiogenesis of human bladder cancer cells with different degrees of malignancy. We analyzed the effects of PSMB4 knockdown in bladder cancer cells and endothelial cells in the tumor microenvironment. PSMB4 was highly expressed in patients with low- and high-grade urothelial carcinoma. Inhibition of PSMB4 reduced protein expression of focal adhesion kinase (FAK) and myosin light chain (MLC), leading to reduced migration. Furthermore, the suppression of PSMB4 decreased the levels of vascular endothelial factor B (VEGF-B), resulting in lower angiogenic abilities in human bladder cancer cells. PSMB4 inhibition affected the migratory ability of HUVECs and reduced VEGFR2 expression, consequently downregulating angiogenesis. In the metastatic animal model, PSMB4 knockdown reduced the relative volumes of lung tumors. Our findings suggest the role of PSMB4 as a potential target for therapeutic strategies against human bladder cancer.</description><subject>Angiogenesis</subject><subject>Animals</subject><subject>Bladder cancer</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cancer cells</subject><subject>Cell adhesion & migration</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - genetics</subject><subject>Cysteine Endopeptidases</subject><subject>Endothelial Cells - metabolism</subject><subject>Endothelial Cells - pathology</subject><subject>Endothelium</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Knockdown Techniques</subject><subject>Human Umbilical Vein Endothelial Cells - metabolism</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Lung cancer</subject><subject>Male</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Neovascularization, Pathologic - genetics</subject><subject>Neovascularization, Pathologic - 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genetics</topic><topic>Cysteine Endopeptidases</topic><topic>Endothelial Cells - metabolism</topic><topic>Endothelial Cells - pathology</topic><topic>Endothelium</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Knockdown Techniques</topic><topic>Human Umbilical Vein Endothelial Cells - metabolism</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Lung cancer</topic><topic>Male</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Neovascularization, Pathologic - genetics</topic><topic>Neovascularization, Pathologic - metabolism</topic><topic>Nitric oxide</topic><topic>Oncology, Experimental</topic><topic>Prevention</topic><topic>Proteasome Endopeptidase Complex - genetics</topic><topic>Proteasome Endopeptidase Complex - metabolism</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>Scientific equipment and supplies industry</topic><topic>Tumor Microenvironment - genetics</topic><topic>Tumors</topic><topic>Urinary Bladder Neoplasms - 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Academic</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lin, Yi-Hsuan</au><au>Chen, Tzu-Min</au><au>Tsai, Yu-Ling</au><au>Tsai, Wen-Chiuan</au><au>Wang, Hisao-Hsien</au><au>Chen, Ying</au><au>Wu, Sheng-Tang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Reduction of PSMB4 in T24 and J82 Bladder Cancer Cells Inhibits the Angiogenesis and Migration of Endothelial Cells</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2024-05-20</date><risdate>2024</risdate><volume>25</volume><issue>10</issue><spage>5559</spage><pages>5559-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Bladder cancer (BC) is a malignant tumor of the urinary system with high mortality and recurrence rates. Proteasome subunit type 4 (PSMB4) is highly expressed and has been identified as having oncogenic properties in a variety of cancer types. This study aimed to explore the effect of PSMB4 knockdown on the survival, migration, and angiogenesis of human bladder cancer cells with different degrees of malignancy. We analyzed the effects of PSMB4 knockdown in bladder cancer cells and endothelial cells in the tumor microenvironment. PSMB4 was highly expressed in patients with low- and high-grade urothelial carcinoma. Inhibition of PSMB4 reduced protein expression of focal adhesion kinase (FAK) and myosin light chain (MLC), leading to reduced migration. Furthermore, the suppression of PSMB4 decreased the levels of vascular endothelial factor B (VEGF-B), resulting in lower angiogenic abilities in human bladder cancer cells. PSMB4 inhibition affected the migratory ability of HUVECs and reduced VEGFR2 expression, consequently downregulating angiogenesis. In the metastatic animal model, PSMB4 knockdown reduced the relative volumes of lung tumors. Our findings suggest the role of PSMB4 as a potential target for therapeutic strategies against human bladder cancer.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>38791597</pmid><doi>10.3390/ijms25105559</doi><orcidid>https://orcid.org/0000-0001-6229-8189</orcidid><orcidid>https://orcid.org/0000-0003-1085-9014</orcidid><orcidid>https://orcid.org/0000-0001-6303-5858</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Angiogenesis Animals Bladder cancer Breast cancer Cancer Cancer cells Cell adhesion & migration Cell Line, Tumor Cell Movement - genetics Cysteine Endopeptidases Endothelial Cells - metabolism Endothelial Cells - pathology Endothelium Female Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Human Umbilical Vein Endothelial Cells - metabolism Humans Hypoxia Lung cancer Male Metastasis Mice Neovascularization, Pathologic - genetics Neovascularization, Pathologic - metabolism Nitric oxide Oncology, Experimental Prevention Proteasome Endopeptidase Complex - genetics Proteasome Endopeptidase Complex - metabolism Protein expression Proteins Scientific equipment and supplies industry Tumor Microenvironment - genetics Tumors Urinary Bladder Neoplasms - genetics Urinary Bladder Neoplasms - metabolism Urinary Bladder Neoplasms - pathology Vascular endothelial growth factor Vascular Endothelial Growth Factor Receptor-2 - genetics Vascular Endothelial Growth Factor Receptor-2 - metabolism |
| title | The Reduction of PSMB4 in T24 and J82 Bladder Cancer Cells Inhibits the Angiogenesis and Migration of Endothelial Cells |
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