Crk adaptor protein-induced phosphorylation of Gab1 on tyrosine 307 via Src is important for organization of focal adhesions and enhanced cell migration

在生长因素刺激之上，支架蛋白质， Gab1，是酷氨酸 phosphorylated 并且随后适配器蛋白质， Crk，从 Gab1 播送信号。我们以前证明了没有细胞外的刺激， Crk overexpression，在各种各样的人的癌症可检测，导致 Gab1 的酷氨酸 phosphorylation。在现在的学习，内在的机制进一步被调查。CrkII 的 Mutational 分析证明 SH2 领域，然而并非 SH3 (N) 或 CrkII 的规章的 Y221 残余，为 Gab1-Y307 phosphorylation 的正式就职是批评的。CrkII 的 SH2 变化也减少了和 Gab1 的相互作用。在 GST 下拉试金，而 Crk-SH3 (N) 与 Gab1 异种交往了， Crk-SH2 跳了到野类型的 Gab1，它缺乏聚类的酷氨酸区域(残余 242-410 ) 。Gab1 的酷氨酸 phosphorylation 被表明适配器的所有 Crk 家庭蛋白质，然而并非另外的包含 SH2 导致。Src 家庭 kinase 禁止者， PP2，废除 Gab1 的导致 Crk 的酷氨酸 phosphorylations。Y307 phosphorylation 在缺乏 Src，是，和 Fyn 的成纤维细胞是无法发现的，甚至在 Crk 的 overexpression 之上，而缺乏仅仅是和 Fyn 的房间仍然与 phosphorylated Y307 包含了 Gab1。而且， Crk 导致了 Src-Y416 的 phosphorylation；因此，在 Crk 和 Csk 之间的相互作用被增加。Gab1-Y307F 异种没能近甚至在 HGF 之上本地化血浆膜刺激和减少的房间移植。而且， Gab1-Y307F 扰乱了 Crk， FAK，和 paxillin 的本地化，它是焦点的粘附的典型部件。一起拿，这些结果显示 Crk 通过 Src 便于 Gab1-Y307 的酷氨酸 phosphorylation，贡献焦点的粘附和提高的房间移植的组织，可能从而支持人的癌症开发。

^(18)F-FDG PET/CT imaging for a gastrointestinal mantle cell lymphoma with multiple lymphomatous polyposis

Multiple lymphomatous polyposis(MLP)is an uncommon type of gastrointestinal lymphoma characterized by the presence of multiple polyps along the gastrointestinal tract.Most of this entity is in fact considered the counterpart of gastrointestinal tract involvement for mantle cell lymphoma(MCL).To our knowledge,there have been no reports on[fluorine-18]-fluorodeoxy-glucose(18F-FDG)-positron emission tomography(PET)/computed tomography(CT)imaging for gastrointestinal MCL with MLP.We present the results of 18F-FDG PET/CT imaging in a patient with gastrointestinal tract involvement of MCL showing continuous MLP from the stomach to the rectum and intestinal intussusception.FDG-PET/CT findings were false negative in typical MLP spreading widely over the gastrointestinal tract,but uptake was noted in large lesions with deep infiltration considered atypical as MLP.On FDG-PET/CT imaging,the Ki-67proliferative index,which is a cell proliferation marker,showed neither correlation with the presence of uptake nor the maximum standardized uptake value.

Adaptor Protein Crk is Implicated in Mucus Formation in Mucinous Epithelial Ovarian Cancer (mEOC) Cells MCAS

Objective： The mucus production is an indicator for the histological grade of mucinous epithelial ovarian cancer （mEOC）. In our previous study, Crk expression was targeted in the human ovarian mucinous adenocarcinoma cell line MCAS through RNA interference, resulting in the establishment of Crk knock down cells. These cells exhibited decreased tumorigenic potential both in vitro and in vivo. The purpose of this study was to investigate if there is any change in the capability of forming mucus in these Crk knock down cells. Methods： Cytoplasmic periodic acid Schiff （PAS） staining and particle excluding assay were conducted to assess the mucus formation within and around cells, respectively. Additionally, the amount of mucus formed in tumor lumps from nude mice model was measured following HE and PAS staining. Results： The increased mucus production in Crk knockdown mEOC cells （MCAS） was manifested by increased number of enlarged cells filled with vacuoles-like mucus observed by phase-contrast microscope and cytoplasmic PAS staining; and enhanced mucus secretion was represented by the assembly of pericellular matrix in particle excluding assay and increased mucus area in tumor lumps from nude mice models. Conclusion： The course of carcinogenesis in mEOC is associated with the altered pattern of mucus production and secretion. The adaptor protein Crk is implicated in both pathways.

Pancreatic Carcinoma with Prominent Mucin Production: A Clinicopathologic and Immunohistochemical Study of 9 Cases

Pancreatic carcinoma occasionally associated with prominent mucin production and this type of tumor designated as PCM (pancreatic carcinoma with prominent mucin production) was diagnosed depends on subjective estimation of the amount of mucous area, and there has been no report on a quantitative evaluation of the amount of mucinous area in the tumor. To examine the feature of PCM, we analyzed 9 cases of PCM among 243 cases of pancreas carcinoma and evaluated the amount of mucin by imaging analysis. Morphologically, 5 cases were classified as intradactal papillary mucinous neoplasms (IPMN)-derived PCM and 4 cases were as ductal adenocarcinoma (DA)-derived PCM. Mucous composition was found to be more than 50% in all IPMN-derived PCM cases, and that was 40% - 50% in DA-derived PCM cases with one exception. IPMN-derived PCM cases showed expansive growth with pancreatic duct dilatation filled with mucin, while DA-derived PCM cases possessed mucin infiltration into interstitial tissue. Immunohisto-chemically, three of 4 DA-derived PCM cases were MUC1(–)/MUC2(+), and the results of expressions for p16 and Dpc4 suggesting that DA-derived PCM was similar to IPMN-derived PCM rather than ordinary DA. Survival rate of DA-derived PCM cases was lower than that of IPMN-derived PCM cases. We advocate that DA-derived PCM may constitute a borderline group between IPMN and ordinary DA.

Numerical Simulation on Inclusion and Bubble Entrapment in Solidified Shell in Model Experiment and in Mold of Continuous Caster With DC Magnetic Field

A model experiment investigating entrapment of inclusions and bubbles on the solidified shell was performed using molten steel,and the conditions for inclusion and bubble entrapment and mechanism of entrapment were studied. The results were applied to the flow behavior in the casting mold of a continuous caster.At the solid-liquid interface, entrapment of inclusions is greatly reduced by the existence of a low velocity flow,e.g.,0.05m/s.The above-mentioned interfacial flow velocity dependency of inclusion entrapment is considered to be largely influenced by changes in the thickness of the concentration boundary layer,which depend on the interfacial flow velocity.Specifically,bubbles and inclusions which enter the concentration boundary layer are drawn to the solid-liquid interface by a suction force which is several orders larger than the Saffman's force.In addition to the above-mentioned suction force,the so-called cleaning effect is determined by fluid-dynamic forces such as drag force,etc.which act on particles,and furthermore,by resident time of particles at the solid-liquid interface,which depends on the solidification rate.In a FC mold with a 2-stage electromagnetic brake,flotation of bubbles entrained in the jet flow from the nozzle is accelerated with the large DC magnetic field.This is attributed to the braking effect of the DC field on the nozzle jet and the upward flow by the buoyancy of the bubbles.As a result,the interfacial flow velocity can be normalized by increasing the strength of the magnetic field,and entrapment of large bubbles and inclusions can be reduced.

miR-23a promotes invasion of glioblastoma via HOXD10-regulated glial-mesenchymal transition

Glioblastoma is the most aggressive and invasive brain tumor and has a poor prognosis;elucidating the underlying molecular mechanisms is essential to select molecular targeted therapies.Here,we investigated the effect of microRNAs on the marked invasiveness of glioblastoma.U373 glioblastoma cells were infected with 140 different microRNAs from an OncomiR library,and the effects of the invasion-related microRNAs and targeted molecules were investigated after repeated Matrigel invasion assays.Screening of the OncomiR library identified miR-23a as a key regulator of glioblastoma invasion.In six glioblastoma cell lines,a positive correlation was detected between the expression levels of miR-23a and invasiveness.A luciferase reporter assay demonstrated that homeobox D10(HOXD10)was a miR-23a-target molecule,which was verified by high scores from both the PicTar and miRanda algorithms.Forced expression of miR-23a induced expression of invasion-related molecules,including uPAR,RhoA,and RhoC,and altered expression of glial-mesenchymal transition markers such as Snail,Slug,MMP2,MMP9,MMP14,and E-cadherin;however,these changes in expression levels were reversed by HOXD10 overexpression.Thus,miR-23a significantly promoted invasion of glioblastoma cells with polarized formation of focal adhesions,while exogenous HOXD10 overexpression reversed these phenomena.Here,we identify miR-23a-regulated HOXD10 as a pivotal regulator of invasion in glioblastoma,providing a novel mechanism for the aggressive invasiveness of this tumor and providing insight into potential therapeutic targets.