There are six core RASSF family proteins that contain conserved Ras Association domains and may serve as Ras effectors. They lack intrinsic enzymatic activity and appear to function as scaffolding and localization molecules. While initially being associated with pro-apoptotic signaling pathways such as Bax and Hippo, it is now clear that they can also connect Ras to a surprisingly broad range of signaling pathways that control senescence, inflammation, autophagy, DNA repair, ubiquitination and protein acetylation. Moreover, they may be able to impact the activation status of pro-mitogenic Ras effector pathways, such as the Raf pathway. The frequent epigenetic inactivation of RASSF genes in human tumors disconnects Ras from pro-death signaling systems, enhancing Ras driven transformation and metastasis. The best characterized members are RASSF1A and RASSF5 (NORE1A).

Brain metastasis is a major contributor to cancer mortality, yet, the genetic changes underlying the development of this capacity remain poorly understood. RASSF proteins are a family of tumor suppressors that often suffer epigenetic inactivation during tumorigenesis. However, their epigenetic status in brain metastases has not been well characterized. We have examined the promoter methylation of the classical RASSF members (RASSF1A-RASSF6) in a panel of metastatic brain tumor samples. RASSF1A and RASSF2 have been shown to undergo promoter methylation at high frequency in primary lung and breast tumors and in brain metastases. Other members exhibited little or no methylation in these tumors. In examining melanoma metastases, however, we found that RASSF6 exhibits the highest frequency of inactivation in melanoma and in melanoma brain metastases. Most melanomas are driven by an activating mutation in B-Raf. Introduction of RASSF6 into a B-Raf(V600E)-containing metastatic melanoma cell line inhibited its ability to invade through collagen and suppressed MAPK pathway activation and AKT. RASSF6 also appears to increase the association of mutant B-Raf and MST1, providing a potential mechanism by which RASSF6 is able to suppress MAPK activation. Thus, we have identified a novel potential role for RASSF6 in melanoma development. Promoter methylation leading to reduced expression of RASSF6 may play an important role in melanoma development and may contribute to brain metastases.

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Some animals express a form of eusociality known as "fortress defense," in which defense rather than brood care is the primary social act. Aphids are small plant-feeding insects, but like termites, some species express division of labor and castes of aggressive juvenile "soldiers." What is the functional basis of fortress defense eusociality in aphids? Previous work showed that the acquisition of venoms might be a key innovation in aphid social evolution. We show that the lethality of aphid soldiers derives in part from the induction of exaggerated immune responses in insects they attack. Comparisons between closely related social and nonsocial species identified a number of secreted effector molecules that are candidates for immune modulation, including a convergently recruited protease described in unrelated aphid species with venom-like functions. These results suggest that aphids are capable of antagonizing conserved features of the insect immune response, and provide new insights into the mechanisms underlying the evolution of fortress defense eusociality in aphids.

Background Pulmonary nodules are a common cause for concern in patients with human immunodeficiency virus and acquired immunodeficiency syndrome. Most commonly, they are the result of an infection, given the patients’ immunocompromised state; however, in some cases, pulmonary nodules in patients with human immunodeficiency virus and patients with acquired immunodeficiency syndrome can result from cellular or protein deposits. We report a rare case of nodular pulmonary light chain deposition disease in a patient with acquired immunodeficiency syndrome and monoclonal gammopathy of undetermined significance. Case presentation A 53-year-old African American woman with acquired immunodeficiency syndrome had pulmonary nodules detected incidentally by imaging of her lungs. Pulmonary tuberculosis was high on the differential diagnosis, but she had a negative test result for pulmonary tuberculosis. Imaging also revealed multiple lucent bone lesions, and earlier in the year, serum protein electrophoresis had shown an immunoglobulin G-kappa monoclonal protein (M spike). She was mildly anemic, so there was concern for progression to myeloma; however, the result of her bone marrow biopsy was unremarkable. Lung biopsy revealed finely granular eosinophilic material with negative Congo red staining, consistent with light chain deposition disease. Conclusions The extent of this patient’s light chain deposition disease was thought to be caused by a combination of acquired immunodeficiency syndrome and monoclonal gammopathy of undetermined significance, and the interval decrease in lung nodule size after restarting antiretroviral therapy confirms this hypothesis and also highlights a potentially unique contribution of the hypergammaglobulinemia to this disease process in patients with human immunodeficiency virus and patients with acquired immunodeficiency syndrome .