User login
ATP-dependent chromatin remodeling is fundamental to DNA metabolism, and SMARCA4 (or BRG1) is the most frequently mutated chromatin remodeling ATPase in cancer.
SMARCA4 is often mutated or silenced in tumors, suggesting a role as tumor suppressor, say researchers from Universidad de Sevilla-Universidad Pablo de Olavide in Spain. However, they note, recent reports show SMARCA4 also is required for tumor cell growth. So they performed a meta-analysis using gene expression, prognosis, and clinicopathologic data to clarify the role of SMARCA4 in cancer.
The researchers concluded that expression of SMARCA4 and another ATPase, SMARCA2, have a “high prognostic value.” Although the SMARCA4 gene is mostly overexpressed in tumors, the researchers say, SMARCA2 is almost invariably downregulated.
The data demonstrate that levels of SMARCA4 and SMARCA2 expression correlate with opposite prognosis in several types of tumors. The SMARCA4 upregulation is associated with a poor prognosis for breast and ovarian cancer, lung adenocarcinoma, liposarcoma, and uveal melanoma, for instance. High expression of SMARCA4 can be used as a prognosis marker for those types of tumors, the researchers say. Exactly how the outcomes are linked to SMARCA4 is not yet clear, but the researchers point to research that found SMARCA4 promotes breast cancer by reprogramming lipid synthesis and is required for maintaining repopulation of hematopoietic stem cells in leukemia. (SMARCA4 is highly expressed in stem cells.)
By contrast, high levels of SMARCA2 expression were associated with a good prognosis in breast and ovarian cancer, lung adenocarcinoma, and liposarcoma.
The researchers say that SMARCA4 expression is mostly associated to cell types that constantly undergo proliferation or self-renewal and SMARCA2 is absent from stem cells and inversely correlated with proliferation in several types of cells, suggesting the “attractive possibility” that they contribute to a type of equilibrium in proliferating-undifferentiated vs quiescent-differentiated conditions. That “antagonistic” behavior, the researchers suggest, should be taken into account when designing specific drugs that target one but not the other ATPase.
Source:
Guerrero-Martínez JA, Reyes JC. Scientific Reports. 2018;8:2043.
doi: 10.1038/s41598-018-20217-3.
ATP-dependent chromatin remodeling is fundamental to DNA metabolism, and SMARCA4 (or BRG1) is the most frequently mutated chromatin remodeling ATPase in cancer.
SMARCA4 is often mutated or silenced in tumors, suggesting a role as tumor suppressor, say researchers from Universidad de Sevilla-Universidad Pablo de Olavide in Spain. However, they note, recent reports show SMARCA4 also is required for tumor cell growth. So they performed a meta-analysis using gene expression, prognosis, and clinicopathologic data to clarify the role of SMARCA4 in cancer.
The researchers concluded that expression of SMARCA4 and another ATPase, SMARCA2, have a “high prognostic value.” Although the SMARCA4 gene is mostly overexpressed in tumors, the researchers say, SMARCA2 is almost invariably downregulated.
The data demonstrate that levels of SMARCA4 and SMARCA2 expression correlate with opposite prognosis in several types of tumors. The SMARCA4 upregulation is associated with a poor prognosis for breast and ovarian cancer, lung adenocarcinoma, liposarcoma, and uveal melanoma, for instance. High expression of SMARCA4 can be used as a prognosis marker for those types of tumors, the researchers say. Exactly how the outcomes are linked to SMARCA4 is not yet clear, but the researchers point to research that found SMARCA4 promotes breast cancer by reprogramming lipid synthesis and is required for maintaining repopulation of hematopoietic stem cells in leukemia. (SMARCA4 is highly expressed in stem cells.)
By contrast, high levels of SMARCA2 expression were associated with a good prognosis in breast and ovarian cancer, lung adenocarcinoma, and liposarcoma.
The researchers say that SMARCA4 expression is mostly associated to cell types that constantly undergo proliferation or self-renewal and SMARCA2 is absent from stem cells and inversely correlated with proliferation in several types of cells, suggesting the “attractive possibility” that they contribute to a type of equilibrium in proliferating-undifferentiated vs quiescent-differentiated conditions. That “antagonistic” behavior, the researchers suggest, should be taken into account when designing specific drugs that target one but not the other ATPase.
Source:
Guerrero-Martínez JA, Reyes JC. Scientific Reports. 2018;8:2043.
doi: 10.1038/s41598-018-20217-3.
ATP-dependent chromatin remodeling is fundamental to DNA metabolism, and SMARCA4 (or BRG1) is the most frequently mutated chromatin remodeling ATPase in cancer.
SMARCA4 is often mutated or silenced in tumors, suggesting a role as tumor suppressor, say researchers from Universidad de Sevilla-Universidad Pablo de Olavide in Spain. However, they note, recent reports show SMARCA4 also is required for tumor cell growth. So they performed a meta-analysis using gene expression, prognosis, and clinicopathologic data to clarify the role of SMARCA4 in cancer.
The researchers concluded that expression of SMARCA4 and another ATPase, SMARCA2, have a “high prognostic value.” Although the SMARCA4 gene is mostly overexpressed in tumors, the researchers say, SMARCA2 is almost invariably downregulated.
The data demonstrate that levels of SMARCA4 and SMARCA2 expression correlate with opposite prognosis in several types of tumors. The SMARCA4 upregulation is associated with a poor prognosis for breast and ovarian cancer, lung adenocarcinoma, liposarcoma, and uveal melanoma, for instance. High expression of SMARCA4 can be used as a prognosis marker for those types of tumors, the researchers say. Exactly how the outcomes are linked to SMARCA4 is not yet clear, but the researchers point to research that found SMARCA4 promotes breast cancer by reprogramming lipid synthesis and is required for maintaining repopulation of hematopoietic stem cells in leukemia. (SMARCA4 is highly expressed in stem cells.)
By contrast, high levels of SMARCA2 expression were associated with a good prognosis in breast and ovarian cancer, lung adenocarcinoma, and liposarcoma.
The researchers say that SMARCA4 expression is mostly associated to cell types that constantly undergo proliferation or self-renewal and SMARCA2 is absent from stem cells and inversely correlated with proliferation in several types of cells, suggesting the “attractive possibility” that they contribute to a type of equilibrium in proliferating-undifferentiated vs quiescent-differentiated conditions. That “antagonistic” behavior, the researchers suggest, should be taken into account when designing specific drugs that target one but not the other ATPase.
Source:
Guerrero-Martínez JA, Reyes JC. Scientific Reports. 2018;8:2043.
doi: 10.1038/s41598-018-20217-3.