METHODS: We retrieved 4 previously reported SMCA, performed additional immunohistochemical and targeted next-generation sequencing (NGS). We also investigated the use of NKX3.1 as a marker for SMCA in the context of its prevalence and extent (using H-score) in a mixed cohort of retrospectively and prospectively tested head and neck lesions (n = 223) and non-neoplastic tissues (n = 66).
RESULTS: NKX3.1 positivity was confirmed in normal mucous acini as well as in mucous acinar class of lesions (5/6, mean H-score: 136.7), including mucinous adenocarcinomas (3/4), SG-IPMN (1/1), and microsecretory adenocarcinoma (MSA) (1/1). All SMCA were positive. Fluorescence in situ hybridization for SS18 rearrangements were negative in all successfully tested cases (0/3). NGS was successful in two cases (cases 3 and 4). Case 3 demonstrated a PTEN c.655C>T p.Q219* mutation and a SEC16A::NOTCH1 fusion while case 4 (clinically aggressive) showed a PTEN c.1026+1G>A p.K342 splice site variant, aTP53 c.524G>A p.R175H mutation and a higher tumor mutation burden (29 per Mb). PTEN immunohistochemical loss was confirmed in both cases and a subset of tumor cells showed strong (extreme) staining for P53 in Case 4.
CONCLUSION: Despite a partial myoepithelial phenotype, SMCA, along with mucinous adenocarcinomas/SG-IPMN and MSA, provisionally constitute a mucous acinar class of tumors based on morphology and NKX3.1 expression. Like salivary mucinous adenocarcinomas/SG-IPMN, SMCA also show alterations of the PTEN/PI3K/AKT pathway and may show progressive molecular alterations. We document the first extramammary tumor with a SEC16A::NOTCH1 fusion.
METHOD: Intriguing evidences discussed the contribution of different intracellular compartments in autophagy membrane formation. Furthermore, autophagy serves to mobilise membranes within cells, thereby promoting cytoplasmic components reorganisation. The intent of this review is to focus on the possibility of autophagy to act as a carrier for GLUT4 through regulating GLUT4 endocytosis, intracellular trafficking in different compartments, and translocation to cell membrane.
RESULTS: The common themes of autophagy and GLUT4 have been highlighted. The review discussed the overlapping of endocytosis mechanism and intracellular compartments, and has shown that autophagy and GLUT4 utilise similar proteins (SNAREs) which are used for exocytosis. On top of that, PI3K and AMPK also control both autophagy and GLUT4.
CONCLUSION: The control of GLUT4 trafficking through autophagy could be a promising field for treating type 2 diabetes.
OBJECTIVE: The aim of this study is an assessment of siRNA-COG3 on proliferation, invasion, and apoptosis of OC cells. In addition, siRNA-COG3 may prevent the growth of OC cancer in mice with tumors.
METHODS: Primary OC cell lines will be treated with siRNA-COG3 to assay YKL40 and identified angiogenesis by Tube-like structure formation in HOMECs. The Golgi morphology was analyzed using Immunofluorescence microscopy. Furthermore, the effects of siRNA-COG3 on the proliferation and apoptosis of cells were evaluated using MTT and TUNEL assays. Clones of the HOSEpiC OC cell line were subcutaneously implanted in FVB/N mice. Mice were treated after two weeks of injection of cells using siRNA-COG3. Tumor development suppression was detected by D-luciferin. RT-PCR and western blotting analyses were applied to determine COG3, MT1- MMP, SNAP23, and YKL40 expression to investigate the effects of COG3 gene knockdown.
RESULTS: siRNA-COG3 exhibited a substantial effect in suppressing tumor growth in mice. It dramatically reduced OC cell proliferation and triggered apoptosis (all p < 0.01). Inhibition of COG3, YKL-40, and MT1-MPP led to suppression of angiogenesis and reduction of microvessel density through SNAP23 in OC cells.
CONCLUSION: Overall, by knockdown of the COG3 gene, MT1-MMP and YKL40 were dropped, leading to suppressed angiogenesis along with decreasing migration and proliferation. SiRNACOG3 may be an ideal agent to consider for clinical trial assessment therapy for OC, especially when an antiangiogenic SNAR-pathway targeting drug.