File Download
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.1186/s13046-018-0998-6
- Scopus: eid_2-s2.0-85059957990
- PMID: 30642390
- WOS: WOS:000455639600001
- Find via
Supplementary
- Citations:
- Appears in Collections:
Article: SOX9 is a dose-dependent metastatic fate determinant in melanoma
Title | SOX9 is a dose-dependent metastatic fate determinant in melanoma |
---|---|
Authors | |
Keywords | SOX9; SOX10 NEDD9 RHOA RAC1 Melanoma Metastatic p21 |
Issue Date | 2019 |
Publisher | BioMed Central Ltd. The Journal's web site is located at http://www.jeccr.com/home |
Citation | Journal of Experimental and Clinical Cancer Research, 2019, v. 38 n. 1, article no. 17, p. 1-19 How to Cite? |
Abstract | Background: In this research, we aimed to resolve contradictory results whether SOX9 plays a positive or negative role in melanoma progression and determine whether SOX9 and its closely related member SOX10 share the same or distinct targets in mediating their functions in melanoma. Methods: Immunofluorescence, TCGA database and qPCR were used to analyze the correlation between the expression patterns and levels of SOX9, SOX10 and NEDD9 in melanoma patient samples. AlamarBlue, transwell invasion and colony formation assays in melanoma cell lines were conducted to investigate the epistatic relationship between SOX10 and NEDD9, as well as the effects of graded SOX9 expression levels. Lung metastasis was determined by tail vein injection assay. Live cell imaging was conducted to monitor dynamics of melanoma migratory behavior. RHOA and RAC1 activation assays measured the activity of Rho GTPases. Results: High SOX9 expression was predominantly detected in patients with distant melanoma metastases whereas SOX10 was present in the different stages of melanoma. Both SOX9 and SOX10 exhibited distinct but overlapping expression patterns with metastatic marker NEDD9. Accordingly, SOX10 was required for NEDD9 expression, which partly mediated its oncogenic functions in melanoma cells. Compensatory upregulation of SOX9 expression in SOX10-inhibited melanoma cells reduced growth and migratory capacity, partly due to elevated expression of cyclin-dependent kinase inhibitor p21 and lack of NEDD9 induction. Conversely, opposite phenomenon was observed when SOX9 expression was further elevated to a range of high SOX9 expression levels in metastatic melanoma specimens, and that high levels of SOX9 can restore melanoma progression in the absence of SOX10 both in vitro and in vivo. In addition, overexpression of SOX9 can also promote invasiveness of the parental melanoma cells by modulating the expression of various matrix metalloproteinases. SOX10 or high SOX9 expression regulates melanoma mesenchymal migration through the NEDD9-mediated focal adhesion dynamics and Rho GTPase signaling. |
Persistent Identifier | http://hdl.handle.net/10722/266384 |
ISSN | 2021 Impact Factor: 12.658 2020 SCImago Journal Rankings: 2.752 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Yang, X | - |
dc.contributor.author | Liang, R | - |
dc.contributor.author | Liu, C | - |
dc.contributor.author | Liu, AJ | - |
dc.contributor.author | Cheung, MPL | - |
dc.contributor.author | Liu, X | - |
dc.contributor.author | Man, OY | - |
dc.contributor.author | Guan, X | - |
dc.contributor.author | Lung, HL | - |
dc.contributor.author | Cheung, MCH | - |
dc.date.accessioned | 2019-01-18T08:18:31Z | - |
dc.date.available | 2019-01-18T08:18:31Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Journal of Experimental and Clinical Cancer Research, 2019, v. 38 n. 1, article no. 17, p. 1-19 | - |
dc.identifier.issn | 1756-9966 | - |
dc.identifier.uri | http://hdl.handle.net/10722/266384 | - |
dc.description.abstract | Background: In this research, we aimed to resolve contradictory results whether SOX9 plays a positive or negative role in melanoma progression and determine whether SOX9 and its closely related member SOX10 share the same or distinct targets in mediating their functions in melanoma. Methods: Immunofluorescence, TCGA database and qPCR were used to analyze the correlation between the expression patterns and levels of SOX9, SOX10 and NEDD9 in melanoma patient samples. AlamarBlue, transwell invasion and colony formation assays in melanoma cell lines were conducted to investigate the epistatic relationship between SOX10 and NEDD9, as well as the effects of graded SOX9 expression levels. Lung metastasis was determined by tail vein injection assay. Live cell imaging was conducted to monitor dynamics of melanoma migratory behavior. RHOA and RAC1 activation assays measured the activity of Rho GTPases. Results: High SOX9 expression was predominantly detected in patients with distant melanoma metastases whereas SOX10 was present in the different stages of melanoma. Both SOX9 and SOX10 exhibited distinct but overlapping expression patterns with metastatic marker NEDD9. Accordingly, SOX10 was required for NEDD9 expression, which partly mediated its oncogenic functions in melanoma cells. Compensatory upregulation of SOX9 expression in SOX10-inhibited melanoma cells reduced growth and migratory capacity, partly due to elevated expression of cyclin-dependent kinase inhibitor p21 and lack of NEDD9 induction. Conversely, opposite phenomenon was observed when SOX9 expression was further elevated to a range of high SOX9 expression levels in metastatic melanoma specimens, and that high levels of SOX9 can restore melanoma progression in the absence of SOX10 both in vitro and in vivo. In addition, overexpression of SOX9 can also promote invasiveness of the parental melanoma cells by modulating the expression of various matrix metalloproteinases. SOX10 or high SOX9 expression regulates melanoma mesenchymal migration through the NEDD9-mediated focal adhesion dynamics and Rho GTPase signaling. | - |
dc.language | eng | - |
dc.publisher | BioMed Central Ltd. The Journal's web site is located at http://www.jeccr.com/home | - |
dc.relation.ispartof | Journal of Experimental and Clinical Cancer Research | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | SOX9; SOX10 | - |
dc.subject | NEDD9 | - |
dc.subject | RHOA | - |
dc.subject | RAC1 | - |
dc.subject | Melanoma | - |
dc.subject | Metastatic | - |
dc.subject | p21 | - |
dc.title | SOX9 is a dose-dependent metastatic fate determinant in melanoma | - |
dc.type | Article | - |
dc.identifier.email | Liu, AJ: jessie11@hku.hk | - |
dc.identifier.email | Cheung, MPL: mplcheun@hku.hk | - |
dc.identifier.email | Guan, X: xyguan@hku.hk | - |
dc.identifier.email | Cheung, MCH: mcheung9@hku.hk | - |
dc.identifier.authority | Guan, X=rp00454 | - |
dc.identifier.authority | Cheung, MCH=rp00245 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1186/s13046-018-0998-6 | - |
dc.identifier.pmid | 30642390 | - |
dc.identifier.pmcid | PMC6330758 | - |
dc.identifier.scopus | eid_2-s2.0-85059957990 | - |
dc.identifier.hkuros | 296710 | - |
dc.identifier.volume | 38 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | article no. 17, p. 1 | - |
dc.identifier.epage | article no. 17, p. 19 | - |
dc.identifier.isi | WOS:000455639600001 | - |
dc.publisher.place | United Kingdom | - |
dc.identifier.issnl | 1756-9966 | - |