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The nuclear-cytoplasmic trafficking of a chromatin-modifying and remodelling protein (KMT2C), in osteosarcoma
Caterina Chiappetta1, Chiara Puggioni1, Raffaella Carletti1
1UOC of Pathology, Department of Medical-Surgical Sciences and Bio-Technologies, Sapienza University of Rome, Latina, Italy.
Abstract:
Osteosarcoma is the most common paediatric primary non-hematopoietic bone tumor; the survival is related to the response to chemotherapy and development of metastases. KMT2C is a chromatin-modifying and remodelling protein and its expression has never been studied in osteosarcoma. The aim of this study was to understand the role of KMT2C in the osteosarcoma carcinogenesis and metastatic progression to identify a new molecular target and to provide new therapeutic approach. We performed the immunohistochemical and gene expression analysis of KMT2C in 32 samples of patients with diagnosis of osteosarcoma with known clinic-pathological data and we analysed the expression of genes involved in the metastatic pathway in four osteosarcoma cell lines by blocking the KMT2C expression using siRNA. We found a nuclear-cytoplamic trafficking of KMT2C and the cytoplasmic localization was higher than the nuclear localization (p < 0.0001). Moreover, the percentage of cells with cytoplasmic positivity increased from low grade primary tissue to metastatic tissues. The cytoplasmic localization of KMT2C could lead to a change in its function supporting osteosarcoma carcinogenesis and progression. Our hypothesis is that KMT2C could affect the enhancer activity of genes influencing the invasive properties and metastatic potential of osteosarcoma.
Insights
The protein KMT2C
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Osteosarcoma is a common pediatric bone cancer where survival depends on chemotherapy response and metastasis.
- The role of KMT2C, a chromatin modifier, in osteosarcoma has not been previously investigated.
- Identifying novel therapeutic targets is crucial for improving osteosarcoma patient outcomes.
Purpose of the Study:
- To investigate the function of KMT2C in osteosarcoma development and metastasis.
- To explore KMT2C as a potential molecular target for new therapeutic strategies.
- To understand the correlation between KMT2C expression patterns and osteosarcoma progression.
Main Methods:
- Immunohistochemical and gene expression analysis of KMT2C in 32 osteosarcoma patient samples.
- Analysis of metastatic pathway genes in osteosarcoma cell lines with KMT2C expression blocked via siRNA.
- Quantitative assessment of KMT2C localization (nuclear vs. cytoplasmic) in tumor tissues.
Main Results:
- KMT2C exhibits significant nuclear-cytoplasmic trafficking, with higher prevalence in the cytoplasm.
- Increased cytoplasmic KMT2C expression correlates with advanced tumor grade and metastatic potential.
- Blocking KMT2C expression affected genes within the metastatic pathway.
Conclusions:
- Cytoplasmic localization of KMT2C may drive osteosarcoma carcinogenesis and metastatic progression.
- KMT2C's role in regulating enhancer activity of genes involved in invasion and metastasis is hypothesized.
- KMT2C represents a promising novel therapeutic target for osteosarcoma treatment.
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