Clusterin in cancer: Dual role as a tumor suppressor gene and an oncogene
Clusterin (CLU), a heterodimeric and sulfated glycoprotein has been associated with various physiological functions. This molecular chaperone protein is ubiquitously expressed in diverse tissues and conserved across species. Differences in subcellular localization and possible existence of different...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2016-01-01
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| Series: | Biomedical Research Journal |
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| Online Access: | http://www.brjnmims.org/article.asp?issn=2349-3666;year=2016;volume=3;issue=2;spage=130;epage=156;aulast=Kadam;type=0 |
| _version_ | 1818434951342718976 |
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| author | Rajashree Kadam Tanuja Teni |
| author_facet | Rajashree Kadam Tanuja Teni |
| author_sort | Rajashree Kadam |
| collection | DOAJ |
| description | Clusterin (CLU), a heterodimeric and sulfated glycoprotein has been associated with various physiological functions. This molecular chaperone protein is ubiquitously expressed in diverse tissues and conserved across species. Differences in subcellular localization and possible existence of different CLU isoforms may contribute to its functional diversity. Increased or decreased expression of CLU has been observed in several cancers versus normal tissues and hence its role in tumorigenesis is controversial. Evidences from several studies imply that CLU may have a dual role as a tumor suppressor gene or an oncogene depending on the signal and cellular context. CLU possibly exerts its oncogenic role by inhibiting apoptosis, activating autophagy and modulating several signaling pathways like IGF-1/IGFR, EGFR, NF-kB, PI3K/AKT, TGFp and select miRNAs. CLU may exert its tumor suppressive effects by regulating cell cycle and inducing apoptosis. In cancer, loss of heterozygosity (LOH), copy number loss at CLU locus, epigenetic modifications and expression of select miRNAs may lead to the downregulation of CLU. Custirsen (OGX-011), a second generation antisense oligonucleotide that inhibits CLU expression and increases sensitivity of cancer cells to chemotherapeutic drugs, is currently in phase III clinical trials. CLU is an attractive target in several cancers, however for effective targeting, it is essential to know whether it acts as an oncogene or a tumor suppressor gene in a specific tissue/cellular context. The current review attempts to discuss the two contrasting roles of CLU in cancer and associated regulatory mechanisms. This review also sheds light on the complex CLU splice variants, the varied functional attributes supporting the dual roles in cancer and limitations of the CLU research that warrant attention. |
| first_indexed | 2024-12-14T16:45:09Z |
| format | Article |
| id | doaj.art-b9941ba20fc34e46a2be5f2c59c07025 |
| institution | Directory Open Access Journal |
| issn | 2349-3666 2349-3674 |
| language | English |
| last_indexed | 2024-12-14T16:45:09Z |
| publishDate | 2016-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Biomedical Research Journal |
| spelling | doaj.art-b9941ba20fc34e46a2be5f2c59c070252022-12-21T22:54:12ZengWolters Kluwer Medknow PublicationsBiomedical Research Journal2349-36662349-36742016-01-013213015610.4103/2349-3666.240609Clusterin in cancer: Dual role as a tumor suppressor gene and an oncogeneRajashree KadamTanuja TeniClusterin (CLU), a heterodimeric and sulfated glycoprotein has been associated with various physiological functions. This molecular chaperone protein is ubiquitously expressed in diverse tissues and conserved across species. Differences in subcellular localization and possible existence of different CLU isoforms may contribute to its functional diversity. Increased or decreased expression of CLU has been observed in several cancers versus normal tissues and hence its role in tumorigenesis is controversial. Evidences from several studies imply that CLU may have a dual role as a tumor suppressor gene or an oncogene depending on the signal and cellular context. CLU possibly exerts its oncogenic role by inhibiting apoptosis, activating autophagy and modulating several signaling pathways like IGF-1/IGFR, EGFR, NF-kB, PI3K/AKT, TGFp and select miRNAs. CLU may exert its tumor suppressive effects by regulating cell cycle and inducing apoptosis. In cancer, loss of heterozygosity (LOH), copy number loss at CLU locus, epigenetic modifications and expression of select miRNAs may lead to the downregulation of CLU. Custirsen (OGX-011), a second generation antisense oligonucleotide that inhibits CLU expression and increases sensitivity of cancer cells to chemotherapeutic drugs, is currently in phase III clinical trials. CLU is an attractive target in several cancers, however for effective targeting, it is essential to know whether it acts as an oncogene or a tumor suppressor gene in a specific tissue/cellular context. The current review attempts to discuss the two contrasting roles of CLU in cancer and associated regulatory mechanisms. This review also sheds light on the complex CLU splice variants, the varied functional attributes supporting the dual roles in cancer and limitations of the CLU research that warrant attention.http://www.brjnmims.org/article.asp?issn=2349-3666;year=2016;volume=3;issue=2;spage=130;epage=156;aulast=Kadam;type=0clusterincancertumor suppressor geneoncogenechaperonestress |
| spellingShingle | Rajashree Kadam Tanuja Teni Clusterin in cancer: Dual role as a tumor suppressor gene and an oncogene Biomedical Research Journal clusterin cancer tumor suppressor gene oncogene chaperone stress |
| title | Clusterin in cancer: Dual role as a tumor suppressor gene and an oncogene |
| title_full | Clusterin in cancer: Dual role as a tumor suppressor gene and an oncogene |
| title_fullStr | Clusterin in cancer: Dual role as a tumor suppressor gene and an oncogene |
| title_full_unstemmed | Clusterin in cancer: Dual role as a tumor suppressor gene and an oncogene |
| title_short | Clusterin in cancer: Dual role as a tumor suppressor gene and an oncogene |
| title_sort | clusterin in cancer dual role as a tumor suppressor gene and an oncogene |
| topic | clusterin cancer tumor suppressor gene oncogene chaperone stress |
| url | http://www.brjnmims.org/article.asp?issn=2349-3666;year=2016;volume=3;issue=2;spage=130;epage=156;aulast=Kadam;type=0 |
| work_keys_str_mv | AT rajashreekadam clusterinincancerdualroleasatumorsuppressorgeneandanoncogene AT tanujateni clusterinincancerdualroleasatumorsuppressorgeneandanoncogene |