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Published on: July 8, 2020
ROCK1 and ROCK2 Are Down-regulated in Aggressive and Advanced Skin Melanomas - A Clinicopathological Perspective
Maciej Kaczorowski1, Przemysław Biecek2, Piotr Donizy3
1Department of Pathomorphology and Oncological Cytology, Wroclaw Medical University, Wroclaw, Poland maciejdkaczorowski@gmail.com.
Background:
RhoA and its downstream effectors Rho-associated coiled-coil kinases (ROCK) 1 and 2 are central controllers of cytoskeleton dynamics, and therefore influence cell shape, adhesion and migration. Since modulation of these processes holds promise for an effective anticancer strategy, effects of ROCK inhibition have been evaluated in a number of malignancies.
Materials And Methods:
Using immunohistochemistry, ROCK1 and ROCK2 expression was semi-quantitatively assessed in 129 patient-derived primary melanomas.
Results:
There was a striking predilection for low melanocytic expression of both kinases in thick, ulcerated and mitogenic tumors, as well as in nodular histological type. ROCK1 and -2 expression in tumor-infiltrating lymphocytes (TILs) was preferentially down-regulated in advanced and aggressive tumors. Moreover, diminished ROCK2 reactivity in melanoma cells and TILs was associated with shorter melanoma-specific and recurrence-free survival.
Conclusion:
This is the first analysis of ROCK1 and -2 protein expression in clinical melanoma samples and the results indicated the suppression of ROCK signaling in melanocytes of aggressive and late-stage tumors. Functional models that more accurately represent the clinical setting are necessary to dissect the role of ROCK1 and -2 in melanoma. Additionally, our study indicates that ROCK activity in TILs may be involved in the pathogenesis of cancer, and thus merits further investigations.
Insights
ROCK (Rho-associated coiled-coil kinase) signaling is suppressed in aggressive melanoma. Reduced ROCK1 and ROCK2 expression in tumor cells and lymphocytes correlates with poorer patient survival, suggesting ROCK
Area of Science:
- Oncology
- Cell Biology
- Cancer Research
Background:
- RhoA and its downstream effectors, Rho-associated coiled-coil kinases (ROCK) 1 and 2, regulate cytoskeleton dynamics, impacting cell shape, adhesion, and migration.
- Modulating these processes is a promising anticancer strategy, with ROCK inhibition explored in various malignancies.
Purpose of the Study:
- To investigate the protein expression levels of ROCK1 and ROCK2 in clinical melanoma samples.
- To correlate ROCK1 and ROCK2 expression with clinicopathological features and patient survival in melanoma.
Main Methods:
- Immunohistochemistry was employed to semi-quantitatively assess ROCK1 and ROCK2 expression.
- The study analyzed 129 patient-derived primary melanoma samples.
Main Results:
- Low melanocytic expression of ROCK1 and ROCK2 was observed in thicker, ulcerated, and mitogenic melanomas, as well as in nodular types.
- ROCK1 and ROCK2 expression in tumor-infiltrating lymphocytes (TILs) was down-regulated in advanced and aggressive tumors.
- Diminished ROCK2 reactivity in both melanoma cells and TILs was associated with shorter melanoma-specific and recurrence-free survival.
Conclusions:
- This study is the first to analyze ROCK1 and ROCK2 protein expression in clinical melanoma, revealing suppressed ROCK signaling in aggressive, late-stage tumors.
- ROCK activity in TILs may play a role in cancer pathogenesis, warranting further investigation.
- Functional models are needed to fully elucidate the role of ROCK1 and ROCK2 in melanoma progression.
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