scholarly journals Ran GTPase is an independent prognostic marker in malignant melanoma which promotes tumour cell migration and invasion

2020 ◽  
pp. jclinpath-2020-206871
Author(s):  
Somaia Elsheikh ◽  
Ilias Kouzoukakis ◽  
Catherine Fielden ◽  
Wei Li ◽  
Shaimaa Elsaid Lashin ◽  
...  
Keyword(s):  
Cell Migration ◽  
Malignant Melanoma ◽  
Cell Motility ◽  
Prognostic Marker ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Functional Activity ◽  
Migration And Invasion ◽  
Ran Gtpase ◽  
Melanoma Cell Lines

AimsRan GTPase is involved in nucleocytoplasmic shuttling of proteins and is overexpressed in several cancers. The expression of Ran in malignant melanoma (MM) and its functional activity have not been described and were investigated in this study.MethodsThe prognostic value of Ran expression was tested in a series of 185 primary cutaneous MM cases using immunohistochemistry. The functional activity of Ran was investigated in the two melanoma cell lines. Ran expression was knocked down using two siRNAs and the effect on the expression of the c-Met oncogene, a potential downstream target of Ran, was tested. Functional effects of Ran knockdown on cell motility and cell proliferation were also assessed.ResultsPositive Ran expression was seen in 12.4% of MM and was associated with advanced clinical stage and greater Breslow thickness. Positive expression was an independent marker of shorter overall survival (p=0.023). Knockdown of Ran results in decreased expression of c-Met and the downstream c-met signalling targets ERK1/2. There was a significant reduction in cell migration (p<0.001) and cell invasion (p<0.001). c-Met knockdown decreased the expression of Ran through MAPK and PI3K-AKT in A375 cell line, inhibited the cell viability and migration of both A375 and G361 melanoma cell lines while invasion was enhanced.ConclusionRan is a poor prognostic marker in cutaneous MM. It upregulates expression of the oncogene c-Met and, possibly through this, it promotes cell motility which may in turn promote metastasis.

scholarly journals Inhibition of Melanoma Cell Migration and Invasion Targeting the Hypoxic Tumor Associated CAXII

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3018
Author(s):  
Gaia Giuntini ◽  
Sara Monaci ◽  
Ylenia Cau ◽  
Mattia Mori ◽  
Antonella Naldini ◽  
...  
Keyword(s):  
Cell Migration ◽  
Malignant Melanoma ◽  
Cell Motility ◽  
Cell Lines ◽  
Cancer Progression ◽  
Melanoma Cell ◽  
Migration And Invasion ◽  
Carbonic Anhydrases ◽  
Cell Migration And Invasion ◽  
Melanoma Cell Lines

Background: Intratumoral hypoxia contributes to cancer progression and poor prognosis. Carbonic anhydrases IX (CAIX) and XII (CAXII) play pivotal roles in tumor cell adaptation and survival, as aberrant Hedgehog (Hh) pathway does. In malignant melanoma both features have been investigated for years, but they have not been correlated before and/or identified as a potential pharmacological target. Here, for the first time, we demonstrated that malignant melanoma cell motility was impaired by targeting CAXII via either CAs inhibitors or through the inhibition of the Hh pathway. Methods: We tested cell motility in three melanoma cell lines (WM-35, SK-MEL28, and A375), with different invasiveness capabilities. To this end we performed a scratch assay in the presence of the smoothened (SMO) antagonist cyclopamine (cyclo) or CAs inhibitors under normoxia or hypoxia. Then, we analyzed the invasiveness potential in the cell lines which were more affected by cyclo and CAs inhibitors (SK-MEL28 and A375). Western blot was employed to assess the expression of the hypoxia inducible factor 1α, CAXII, and FAK phosphorylation. Immunofluorescence staining was performed to verify the blockade of CAXII expression. Results: Hh inhibition reduced melanoma cell migration and CAXII expression under both normoxic and hypoxic conditions. Interestingly, basal CAXII expression was higher in the two more aggressive melanoma cell lines. Finally, a direct CAXII blockade impaired melanoma cell migration and invasion under hypoxia. This was associated with a decrease of FAK phosphorylation and metalloprotease activities. Conclusions: CAXII may be used as a target for melanoma treatment not only through its direct inhibition, but also through Hh blockade.

scholarly journals Analysis of Malignant Melanoma Cell Lines Exposed to Hypoxia Reveals the Importance of PFKFB4 Overexpression for Disease Progression

2018 ◽  
Vol 38 (12) ◽  
pp. 6745-6752 ◽  
Author(s):  
SONIA E. TROJAN ◽  
MONIKA PIWOWAR ◽  
BARBARA OSTROWSKA ◽  
PIOTR LAIDLER ◽  
KINGA A. KOCEMBA-PILARCZYK
Keyword(s):  
Malignant Melanoma ◽  
Disease Progression ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Malignant Melanoma Cell ◽  
Melanoma Cell Lines

scholarly journals Tumour Progression Stage-Dependent Secretion of YB-1 Stimulates Melanoma Cell Migration and Invasion

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2328 ◽  
Author(s):  
Corinna Kosnopfel ◽  
Tobias Sinnberg ◽  
Birgit Sauer ◽  
Heike Niessner ◽  
Alina Muenchow ◽  
...  
Keyword(s):  
Cell Migration ◽  
Malignant Melanoma ◽  
Melanoma Cell ◽  
Cell Biology ◽  
Secretory Pathway ◽  
Tumour Progression ◽  
Melanoma Cells ◽  
Migration And Invasion ◽  
Melanoma Progression ◽  
And Migration

Secreted factors play an important role in intercellular communication. Therefore, they are not only indispensable for the regulation of various physiological processes but can also decisively advance the development and progression of tumours. In the context of inflammatory disease, Y-box binding protein 1 (YB-1) is actively secreted and the extracellular protein promotes cell proliferation and migration. In malignant melanoma, intracellular YB-1 expression increases during melanoma progression and represents an unfavourable prognostic marker. Here, we show active secretion of YB-1 from melanoma cells as opposed to benign cells of the skin. Intriguingly, YB-1 secretion correlates with the stage of melanoma progression and depends on a calcium- and ATP-dependent non-classical secretory pathway leading to the occurrence of YB-1 in the extracellular space as a free protein. Along with an elevated YB-1 secretion of melanoma cells in the metastatic growth phase, extracellular YB-1 exerts a stimulating effect on melanoma cell migration, invasion, and tumourigenicity. Collectively, these data suggest that secreted YB-1 plays a functional role in melanoma cell biology, stimulating metastasis, and may serve as a novel biomarker in malignant melanoma that reflects tumour aggressiveness.

Mutation and expression of the p53 gene in malignant melanoma cell lines

1993 ◽  
Vol 54 (4) ◽  
pp. 693-699 ◽  
Author(s):  
Jürgen Weiss ◽  
Karl Schwechheimer ◽  
Webster K. Cavenee ◽  
Meenhard Herlyn ◽  
Karen C. Arden
Keyword(s):  
Malignant Melanoma ◽  
Cell Lines ◽  
Melanoma Cell ◽  
P53 Gene ◽  
Malignant Melanoma Cell ◽  
Melanoma Cell Lines
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