Sedoheptulose kinase SHPK expression in glioblastoma: emerging role of the nonoxidative pentose phosphate pathway in tumor proliferation
Glioblastoma (GBM) is the most common form of malignant brain cancer and is considered the deadliest human cancer. Because of poor outcomes in this disease, there is an urgent need for progress in understanding the molecular mechanisms of GBM therapeutic resistance, as well as novel and innovative t...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
MDPI
2022
|
| _version_ | 1826308086639362048 |
|---|---|
| author | Franceschi, S Lessi, F Morelli, M Menicagli, M Pasqualetti, F Aretini, P Mazzanti, CM |
| author_facet | Franceschi, S Lessi, F Morelli, M Menicagli, M Pasqualetti, F Aretini, P Mazzanti, CM |
| author_sort | Franceschi, S |
| collection | OXFORD |
| description | Glioblastoma (GBM) is the most common form of malignant brain cancer and is considered the deadliest human cancer. Because of poor outcomes in this disease, there is an urgent need for progress in understanding the molecular mechanisms of GBM therapeutic resistance, as well as novel and innovative therapies for cancer prevention and treatment. The pentose phosphate pathway (PPP) is a metabolic pathway complementary to glycolysis, and several PPP enzymes have already been demonstrated as potential targets in cancer therapy. In this work, we aimed to evaluate the role of sedoheptulose kinase (SHPK), a key regulator of carbon flux that catalyzes the phosphorylation of sedoheptulose in the nonoxidative arm of the PPP. SHPK expression was investigated in patients with GBM using microarray data. SHPK was also overexpressed in GBM cells, and functional studies were conducted. SHPK expression in GBM shows a significant correlation with histology, prognosis, and survival. In particular, its increased expression is associated with a worse prognosis. Furthermore, its overexpression in GBM cells confirms an increase in cell proliferation. This work highlights for the first time the importance of SHPK in GBM for tumor progression and proposes this enzyme and the nonoxidative PPP as possible therapeutic targets. |
| first_indexed | 2024-03-07T07:12:46Z |
| format | Journal article |
| id | oxford-uuid:b7f3ca65-48d4-4a97-b5af-a36e537851dd |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:12:46Z |
| publishDate | 2022 |
| publisher | MDPI |
| record_format | dspace |
| spelling | oxford-uuid:b7f3ca65-48d4-4a97-b5af-a36e537851dd2022-07-11T12:02:49ZSedoheptulose kinase SHPK expression in glioblastoma: emerging role of the nonoxidative pentose phosphate pathway in tumor proliferationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b7f3ca65-48d4-4a97-b5af-a36e537851ddEnglishSymplectic ElementsMDPI2022Franceschi, SLessi, FMorelli, MMenicagli, MPasqualetti, FAretini, PMazzanti, CMGlioblastoma (GBM) is the most common form of malignant brain cancer and is considered the deadliest human cancer. Because of poor outcomes in this disease, there is an urgent need for progress in understanding the molecular mechanisms of GBM therapeutic resistance, as well as novel and innovative therapies for cancer prevention and treatment. The pentose phosphate pathway (PPP) is a metabolic pathway complementary to glycolysis, and several PPP enzymes have already been demonstrated as potential targets in cancer therapy. In this work, we aimed to evaluate the role of sedoheptulose kinase (SHPK), a key regulator of carbon flux that catalyzes the phosphorylation of sedoheptulose in the nonoxidative arm of the PPP. SHPK expression was investigated in patients with GBM using microarray data. SHPK was also overexpressed in GBM cells, and functional studies were conducted. SHPK expression in GBM shows a significant correlation with histology, prognosis, and survival. In particular, its increased expression is associated with a worse prognosis. Furthermore, its overexpression in GBM cells confirms an increase in cell proliferation. This work highlights for the first time the importance of SHPK in GBM for tumor progression and proposes this enzyme and the nonoxidative PPP as possible therapeutic targets. |
| spellingShingle | Franceschi, S Lessi, F Morelli, M Menicagli, M Pasqualetti, F Aretini, P Mazzanti, CM Sedoheptulose kinase SHPK expression in glioblastoma: emerging role of the nonoxidative pentose phosphate pathway in tumor proliferation |
| title | Sedoheptulose kinase SHPK expression in glioblastoma: emerging role of the nonoxidative pentose phosphate pathway in tumor proliferation |
| title_full | Sedoheptulose kinase SHPK expression in glioblastoma: emerging role of the nonoxidative pentose phosphate pathway in tumor proliferation |
| title_fullStr | Sedoheptulose kinase SHPK expression in glioblastoma: emerging role of the nonoxidative pentose phosphate pathway in tumor proliferation |
| title_full_unstemmed | Sedoheptulose kinase SHPK expression in glioblastoma: emerging role of the nonoxidative pentose phosphate pathway in tumor proliferation |
| title_short | Sedoheptulose kinase SHPK expression in glioblastoma: emerging role of the nonoxidative pentose phosphate pathway in tumor proliferation |
| title_sort | sedoheptulose kinase shpk expression in glioblastoma emerging role of the nonoxidative pentose phosphate pathway in tumor proliferation |
| work_keys_str_mv | AT franceschis sedoheptulosekinaseshpkexpressioninglioblastomaemergingroleofthenonoxidativepentosephosphatepathwayintumorproliferation AT lessif sedoheptulosekinaseshpkexpressioninglioblastomaemergingroleofthenonoxidativepentosephosphatepathwayintumorproliferation AT morellim sedoheptulosekinaseshpkexpressioninglioblastomaemergingroleofthenonoxidativepentosephosphatepathwayintumorproliferation AT menicaglim sedoheptulosekinaseshpkexpressioninglioblastomaemergingroleofthenonoxidativepentosephosphatepathwayintumorproliferation AT pasqualettif sedoheptulosekinaseshpkexpressioninglioblastomaemergingroleofthenonoxidativepentosephosphatepathwayintumorproliferation AT aretinip sedoheptulosekinaseshpkexpressioninglioblastomaemergingroleofthenonoxidativepentosephosphatepathwayintumorproliferation AT mazzanticm sedoheptulosekinaseshpkexpressioninglioblastomaemergingroleofthenonoxidativepentosephosphatepathwayintumorproliferation |