The role of endoplasmic reticulum stress in maintaining and targeting multiple myeloma: a double-edged sword of adaptation and apoptosis
Increased cellular protein production places stress on the endoplasmic reticulum (ER), because many of the nascent proteins pass through the ER for folding and trafficking. Accumulation of misfolded proteins in the ER triggers the activation of three well-known pathways including IRE1, ATF6, and PE...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2013-06-01
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| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fgene.2013.00109/full |
| _version_ | 1819060823607214080 |
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| author | Shai eWhite-Gilbertson Yunpeng eHua Bei eLiu |
| author_facet | Shai eWhite-Gilbertson Yunpeng eHua Bei eLiu |
| author_sort | Shai eWhite-Gilbertson |
| collection | DOAJ |
| description | Increased cellular protein production places stress on the endoplasmic reticulum (ER), because many of the nascent proteins pass through the ER for folding and trafficking. Accumulation of misfolded proteins in the ER triggers the activation of three well-known pathways including IRE1, ATF6, and PERK. The activity of each sensor modulates the overall ER strategy for managing protein quality control as cellular needs change due to growth, differentiation, infection, transformation, and host of other possible physiological states. Here we review the role of ER stress in multiple myeloma (MM), an incurable plasma cell neoplasm. MM is closely linked to dysregulated unfolded protein response in ER due to the heightened production of immunoglobulin and the metabolic demands of malignant uncontrolled proliferation. Together, these forces may mean that myeloma cells have an Achilles heel which can be exploited as a treatment target: their ER stress response must be constitutively active at a remarkably high level to survive their unique metabolic needs. Therefore, inhibition of the ER stress response is likely to injure the cells, as is any further demand on an already over-worked system. Evidence for this vulnerability is summarized here, along with an overview of how each of the three ER stress sensors has been implicated in myeloma pathogenesis and treatment. |
| first_indexed | 2024-12-21T14:33:07Z |
| format | Article |
| id | doaj.art-3e44030754b04afb8a973f95a67b6245 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-21T14:33:07Z |
| publishDate | 2013-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-3e44030754b04afb8a973f95a67b62452022-12-21T19:00:25ZengFrontiers Media S.A.Frontiers in Genetics1664-80212013-06-01410.3389/fgene.2013.0010952799The role of endoplasmic reticulum stress in maintaining and targeting multiple myeloma: a double-edged sword of adaptation and apoptosisShai eWhite-Gilbertson0Yunpeng eHua1Bei eLiu2Medical University of South CarolinaMedical University of South CarolinaMedical University of South CarolinaIncreased cellular protein production places stress on the endoplasmic reticulum (ER), because many of the nascent proteins pass through the ER for folding and trafficking. Accumulation of misfolded proteins in the ER triggers the activation of three well-known pathways including IRE1, ATF6, and PERK. The activity of each sensor modulates the overall ER strategy for managing protein quality control as cellular needs change due to growth, differentiation, infection, transformation, and host of other possible physiological states. Here we review the role of ER stress in multiple myeloma (MM), an incurable plasma cell neoplasm. MM is closely linked to dysregulated unfolded protein response in ER due to the heightened production of immunoglobulin and the metabolic demands of malignant uncontrolled proliferation. Together, these forces may mean that myeloma cells have an Achilles heel which can be exploited as a treatment target: their ER stress response must be constitutively active at a remarkably high level to survive their unique metabolic needs. Therefore, inhibition of the ER stress response is likely to injure the cells, as is any further demand on an already over-worked system. Evidence for this vulnerability is summarized here, along with an overview of how each of the three ER stress sensors has been implicated in myeloma pathogenesis and treatment.http://journal.frontiersin.org/Journal/10.3389/fgene.2013.00109/fullApoptosisEndoplasmic ReticulumMultiple MyelomaUnfolded Protein Responseer stress |
| spellingShingle | Shai eWhite-Gilbertson Yunpeng eHua Bei eLiu The role of endoplasmic reticulum stress in maintaining and targeting multiple myeloma: a double-edged sword of adaptation and apoptosis Frontiers in Genetics Apoptosis Endoplasmic Reticulum Multiple Myeloma Unfolded Protein Response er stress |
| title | The role of endoplasmic reticulum stress in maintaining and targeting multiple myeloma: a double-edged sword of adaptation and apoptosis |
| title_full | The role of endoplasmic reticulum stress in maintaining and targeting multiple myeloma: a double-edged sword of adaptation and apoptosis |
| title_fullStr | The role of endoplasmic reticulum stress in maintaining and targeting multiple myeloma: a double-edged sword of adaptation and apoptosis |
| title_full_unstemmed | The role of endoplasmic reticulum stress in maintaining and targeting multiple myeloma: a double-edged sword of adaptation and apoptosis |
| title_short | The role of endoplasmic reticulum stress in maintaining and targeting multiple myeloma: a double-edged sword of adaptation and apoptosis |
| title_sort | role of endoplasmic reticulum stress in maintaining and targeting multiple myeloma a double edged sword of adaptation and apoptosis |
| topic | Apoptosis Endoplasmic Reticulum Multiple Myeloma Unfolded Protein Response er stress |
| url | http://journal.frontiersin.org/Journal/10.3389/fgene.2013.00109/full |
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