RalB Signaling: A Bridge between Inflammation and Cancer
ABSTRACT A connection between the genetic events that lead to tumor formation and the signaling pathways of the innate immune response has been established. In this issue, Chien et al. (2006) show that the RalB GTPase regulates the IKK family member TBK1, providing an unexpected link between the signaling pathways that promote inflammation and cancer. In tumor cells the RalB/TBK1 pathway inhibits apoptosis and in nontumorigenic cells it stimulates an innate immune response.
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ABSTRACT: Several studies have demonstrated that cancer can develop with the contribution of bone marrow-derived cancer stem cells. We evaluated the possible involvement of bone marrow-derived stem cells in hepatocarcinogenesis in a hepatitis B virus (HBV) transgenic mouse model. Bone marrow cells from wild type male mice were transplanted into sublethally irradiated, female, HBV transgenic mice with hepatocarcinoma nodules. Four months later, liver tissue was examined to localize neoplastic nodules/foci and characterize cells by evaluating the Y-chromosome and the hepatocyte lineage marker hepatocyte nuclear factor-1 (HNF1), as well as the HBsAg encoding gene (HBs-Eg) and HBsAg protein (HBs-Pr) (present only in cells of female origin). Hepatocytes were HBs-Eg/HBs-Pr-positive in "normal" tissue, while resulted only HBs-Eg-positive in regenerative areas. Neoplastic foci/nodules were both HBs-Eg/HBs-Pr-negative. In the liver, 19±5% of cells were Y-chromosome-positive and about one fifth were HNF1-positive. Y-chromosome and HBs-Eg colocalized in HNF1-positive cells. Y-chromosome-positive cells never localized in neoplastic foci/nodules (HBs-Pr/HBs-Eg-negative). Bone marrow-derived stem cells participate in the hepatic regenerative process but not in neoplastic growth. Simultaneous detection of both Y-chromosome and HBs-Eg in the nucleus of an HNF1-positive cell (hepatocyte) demonstrates a phenomenon of cell fusion.Digestive and Liver Disease 11/2013; 46(3). DOI:10.1016/j.dld.2013.10.008 · 2.89 Impact Factor
- Gastroenterology 01/2011; 140(5). DOI:10.1016/S0016-5085(11)63448-3 · 13.93 Impact Factor