Background: Metastasis of rhabdomyosarcoma (RMS) is the primary cause of tumour-related deaths. Previous studies have shown that overexpression of the guanine nucleotide exchange factor T (GEFT) is correlated with a poorer RMS prognosis, but the mechanism remains largely unexplored. Methods: We focused on determining the influence of the GEFT-Rho-GTPase signalling pathway and the epi-thelialÀmesenchymal transition (EMT) or mesenchymalÀepithelial transition (MET) on RMS progression and metastasis by using RMS cell lines, BALB/c nude mice and cells and molecular biology techniques. Findings: GEFT promotes RMS cell viability, migration, and invasion; GEFT also inhibits the apoptosis of RMS cells and accelerates the growth and lung metastasis of RMS by activating the Rac1/Cdc42 pathways. Interestingly, GEFT upregulates the expression levels of N-cadherin, Snail, Slug, Twist, Zeb1, and Zeb2 and reduces expression level of E-cadherin. Thus, GEFT influences the expression of markers for EMT and MET in RMS cells via the Rac1/Cdc42-PAK1 pathways. We also found that the level of GEFT gene promoter methylation in RMS is lower than that in normal striated muscle tissue. Significant differences were observed in the level of GEFT gene methylation in different histological subtypes of RMS. Interpretation: These findings suggest that GEFT accelerates the tumourigenicity and metastasis of RMS by activating Rac1/Cdc42-PAK signalling pathway-induced EMT; thus, it may serve as a novel therapeutic target.

Perilipins, an ancient family of lipid droplet-associated proteins, are embedded in a phospho-lipid monolayer of intracellular lipid droplets. The core of lipid droplets is composed of neutral fat, which mainly includes triglyceride and cholesterol ester. Perilipins are closely related to the function of lipid droplets, and they mediate lipid metabolism and storage. Therefore, perilipins play an important role in the development of obesity, diabetes, cancer, hepatic diseases, atherosclerosis, and carcinoma, which are caused by abnormal lipid metabolism. Accumulation of lipid droplets is a common phenomenon in tumor cells. Available data on the pathophysiology of perilipins and the relationship of perilipins with endocrine metabolic diseases and cancers are summarized in this mini-review. The research progress on this family offers novel insights into the therapeutic strategies for these diseases.

Objective: Liposarcoma is a mesenchymal malignant tumor characterized by adipocyte differentiation which is divided into four subtypes with different prognosis. Accurate histopathological diagnosis is essential for precise treatment. Perilipins, including PLIN1, PLIN2, PLIN3, PLIN4, PLIN5, is a family of lipid droplet-associated proteins that participate in lipid metabolism regulation. The role that perilipins play in sarcomas is not clear. This study aims to assess perilipins expression in subtypes of liposarcoma and various non-lipomatous sarcomas. Methods:A large set of 245 soft tissue sarcoma paraffin-embedded samples including 66 liposarcomas and 179 non-lipomatous sarcomas were collected for tissue microarray and immunohistochemistry to assess perilipins expression.Results: PLIN1 expression was shown in most liposarcomas (41/66) and was absent in non-lipomatous sarcomas (0/179). PLIN4 expression was shown in some liposarcomas (21/66) and was almost negative in non-lipomatous sarcomas (2/179). PLIN1 and PLIN4 expressions in liposarcoma were higher (both P<0.001) than those in non-lipomatous sarcoma. Both PLIN1 and PLIN4 also had a significant difference in liposarcoma subtypes (both P<0.001). PLIN2, PLIN3 and PLIN5 were widely expressed in liposarcomas, rhabdomyosarcomas, leiomyosarcomas, dermatofibrosarcoma protuberans, undifferentiated sarcomas, fibrosarcomas, Ewing's sarcomas and epithelioid sarcomas. PLIN2, PLIN3 and PLIN5 expressions were significantly different among non-lipomatous sarcoma (all P<0.01). Except for PLIN3, the expression of the other four perilipin members in liposarcoma was pairwise related.Conclusions: PLIN1 and PLIN4 can be used as diagnostic markers of liposarcoma and to differentiate liposarcoma subtypes. The combined application of whole perilipin family immunohistochemistry may help to distinguish differently differentiated sarcomas.

Isolated intracranial myeloid sarcoma (MS) is an unusual variant tumor with few cases reported so far in the medical literature. A 29-year-old woman was admitted to our hospital presenting progressive visual loss in the right eye and weight loss (20 kg) without a previous history of hematological disease (HD). Radiologic evaluation showed the evidence of intracranial mass. Histologically, the resected tumor was composed of a uniform population of primitive cells and primarily misdiagnosed as a T-cell non-Hodgkin's lymphoma (NHL). Chemotherapy with cyclophosphamide, doxorubicin, vinblastine, and prednisone (CHOP) was ineffective. A biopsy and histopathological evaluation were repeated, and immunohistochemical staining revealed the positivity of immature cells to an extensive panel of myeloid markers. These findings were consistent with a diagnosis of MS and bone marrow infiltration. Literature reviews of previous cases were also undertaken.

Autophagy and apoptosis are dynamic processes that determine the fate of cells, and regulating these processes can treat cancer. GEFT is highly expressed in rhabdomyosarcoma (RMS), which accelerates the tumorigenicity and metastasis of RMS by activating Rac1/Cdc42 signaling, but the regulatory mechanisms of autophagy and apoptosis are unclear. In our study, we found that the RMS tissues had high Rac1, Cdc42, mTOR, and Bcl-2 expression levels and low Beclin1, LC3, and Bax expression levels compared with the normal striated muscle tissues (P &lt; 0.05). In addition, multivariate analysis has proven that Rac1 is an independent prognostic factor (P &lt; 0.05), and the high expression level of the Beclin1 protein was closely associated with the tumor diameter of the RMS patients (P = 0.044), whereas the high expression level of the LC3 protein was associated with the clinical stage of the RMS patients (P = 0.027). Furthermore, GEFT overexpression could inhibit autophagy and apoptosis in RMS. A Rac1/Cdc42 inhibitor was added, and the inhibition of autophagy and apoptosis decreased. Rac1 and Cdc42 could regulate mTOR to inhibit autophagy and apoptosis in RMS. Overall, these studies demonstrated that the GEFT–Rac1/Cdc42–mTOR pathway can inhibit autophagy and apoptosis in RMS and provide evidence for innovative treatments.