ALK signaling cascade confers multiple advantages to glioblastoma cells through neovascularization and cell proliferation Article Swipe
Risako Chiba
,
Masashi Akiya
,
Miki Hashimura
,
Yasuko Oguri
,
Madoka Inukai
,
Atsuko Hara
,
Makoto Saegusa
·
YOU?
·
· 2017
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pone.0183516
YOU?
·
· 2017
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pone.0183516
Anaplastic lymphoma kinase (ALK), which is a receptor tyrosine kinase, is essentially and transiently expressed in the developing nervous system. Here we examined the functional role of the ALK gene in glioblastomas (GBMs). In clinical samples of GBMs, high ALK expression without gene rearrangements or mutations was frequently observed in perivascular lesions, in contrast to the relatively low expression in the perinecrotic areas, which was positively correlated with N-myc and phosphorylated (p) Stat3 scores and Ki-67 labeling indices. ALK immunoreactivity was also found to be associated with neovascular features including vascular co-option and vascular mimicry. In astrocytoma cell lines, cells stably overexpressing full-length ALK showed an increase in expression of pStat3 and pAkt proteins, as well as hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A) mRNAs, in contrast to cells with knockdown of endogenous ALK which showed decreased expression of these molecules. Transfection of the constitutively active form of Stat3 induced an increase in HIF-1α promoter activity, and the overexpression of HIF-1α in turn resulted in enhancement of VEGF-A promoter activity. In addition, cells with overexpression or knockdown of ALK also showed a tendency toward increased and decreased proliferation, respectively, through changes in expression of pAkt and pStat3. Finally, ALK promoter was significantly activated by transfection of Sox4 and N-myc, which are known to contribute to neuronal properties. These findings therefore suggest that N-myc/Sox4-mediated ALK signaling cascades containing Stat3, Akt, HIF-1α, and VEGF-A confer multiple advantages to tumor growth through alterations in neovascularization and cell proliferation in GBMs.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1371/journal.pone.0183516
- https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0183516&type=printable
- OA Status
- gold
- Cited By
- 37
- References
- 45
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2746522122
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2746522122Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1371/journal.pone.0183516Digital Object Identifier
- Title
-
ALK signaling cascade confers multiple advantages to glioblastoma cells through neovascularization and cell proliferationWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2017Year of publication
- Publication date
-
2017-08-24Full publication date if available
- Authors
-
Risako Chiba, Masashi Akiya, Miki Hashimura, Yasuko Oguri, Madoka Inukai, Atsuko Hara, Makoto SaegusaList of authors in order
- Landing page
-
https://doi.org/10.1371/journal.pone.0183516Publisher landing page
- PDF URL
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https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0183516&type=printableDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0183516&type=printableDirect OA link when available
- Concepts
-
Gene knockdown, Cancer research, Anaplastic lymphoma kinase, Transfection, Biology, Protein kinase B, Cell growth, Molecular biology, STAT3, Signal transduction, Vascular endothelial growth factor, Cell culture, Cell biology, Pathology, Medicine, Lung cancer, Malignant pleural effusion, VEGF receptors, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
37Total citation count in OpenAlex
- Citations by year (recent)
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2025: 1, 2024: 4, 2023: 15, 2022: 3, 2021: 7Per-year citation counts (last 5 years)
- References (count)
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45Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.frequently | 47 |
| abstract_inverted_index.functional | 24 |
| abstract_inverted_index.molecules. | 142 |
| abstract_inverted_index.positively | 65 |
| abstract_inverted_index.relatively | 56 |
| abstract_inverted_index.alterations | 241 |
| abstract_inverted_index.astrocytoma | 96 |
| abstract_inverted_index.endothelial | 122 |
| abstract_inverted_index.enhancement | 167 |
| abstract_inverted_index.essentially | 11 |
| abstract_inverted_index.full-length | 102 |
| abstract_inverted_index.neovascular | 87 |
| abstract_inverted_index.properties. | 218 |
| abstract_inverted_index.transiently | 13 |
| abstract_inverted_index.Transfection | 143 |
| abstract_inverted_index.perinecrotic | 61 |
| abstract_inverted_index.perivascular | 50 |
| abstract_inverted_index.transfection | 206 |
| abstract_inverted_index.glioblastomas | 31 |
| abstract_inverted_index.proliferation | 246 |
| abstract_inverted_index.respectively, | 190 |
| abstract_inverted_index.significantly | 203 |
| abstract_inverted_index.constitutively | 146 |
| abstract_inverted_index.overexpressing | 101 |
| abstract_inverted_index.overexpression | 160, 176 |
| abstract_inverted_index.phosphorylated | 70 |
| abstract_inverted_index.proliferation, | 189 |
| abstract_inverted_index.rearrangements | 43 |
| abstract_inverted_index.immunoreactivity | 79 |
| abstract_inverted_index.hypoxia-inducible | 117 |
| abstract_inverted_index.neovascularization | 243 |
| abstract_inverted_index.N-myc/Sox4-mediated | 224 |
| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 90 |
| corresponding_author_ids | https://openalex.org/A5001260734, https://openalex.org/A5018603087, https://openalex.org/A5053739464, https://openalex.org/A5012012122, https://openalex.org/A5024022304, https://openalex.org/A5049405145, https://openalex.org/A5009292470 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 7 |
| corresponding_institution_ids | https://openalex.org/I64189623 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.5699999928474426 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.77212847 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |