Eppley Institute for Research in Cancer and Allied Diseases

About: Eppley Institute for Research in Cancer and Allied Diseases is a based out in . It is known for research contribution in the topics: Pancreatic cancer & Cancer. The organization has 965 authors who have published 1396 publications receiving 58994 citations.

Endosomal-sorting complexes required for transport (ESCRT) pathway-dependent endosomal traffic regulates the localization of active Src at focal adhesions

Abstract: Active Src localization at focal adhesions (FAs) is essential for cell migration. How this pool is linked mechanistically to the large pool of Src at late endosomes (LEs)/lysosomes (LY) is not well understood. Here, we used inducible Tsg101 gene deletion, TSG101 knockdown, and dominant-negative VPS4 expression to demonstrate that the localization of activated cellular Src and viral Src at FAs requires the endosomal-sorting complexes required for transport (ESCRT) pathway. Tsg101 deletion also led to impaired Src-dependent activation of STAT3 and focal adhesion kinase and reduced cell migration. Impairment of the ESCRT pathway or Rab7 function led to the accumulation of active Src at aberrant LE/LY compartments followed by its loss. Analyses using fluorescence recovery after photo-bleaching show that dynamic mobility of Src in endosomes is ESCRT pathway-dependent. These results reveal a critical role for an ESCRT pathway-dependent LE/LY trafficking step in Src function by promoting localization of active Src to FAs.

Expression of nerve growth factors in pancreatic neural tissue and pancreatic cancer.

Abstract: One of the characteristics of pancreatic cancer is its tendency to invade neural tissue. We hypothesized that the affinity of cancer cells for nerve tissue is related to the presence of growth factors in neural tissue and their receptors in cancer cells. Sections of pancreatic cancer and normal pancreatic tissue were examined by immunohistochemistry for the expression of the neurotrophins NGF, BDNF, NT-3, NT-4, and their receptors TrkA, TrkB, and TrkC, as well as the low-affinity receptor, p75NTR. TrkA expression was found in duct, islet, and cancer cells; TrkB was found in the alpha-cells of the islet only. The anti-pan-Trk antibody (TrkB3), which is presumed to recognize all three receptors, immunoreacted with duct and acinar cells in normal tissue and with cancer cells. The staining with TrkC was similar to that of TrkA. The low-affinity receptor p75NTR was expressed in the neural tissue and in scattered duct cells of the normal tissue only. Duct and acinar cells, as well as neural tissue and cancer cells, showed weak to strong immunoreactivity with NGF. NT-3 expression was noted in capillary endothelia and erythrocytes. NT-4 showed specific staining for ductule cells. The expression and distribution of neurotrophins and their receptors suggest their role in the potential of pancreatic cancer cells for neural invasion.

Carboxyl-terminal domain of MUC16 imparts tumorigenic and metastatic functions through nuclear translocation of JAK2 to pancreatic cancer cells

Abstract: // Srustidhar Das 1 , Satyanarayana Rachagani 1,* , Maria P. Torres-Gonzalez 1,* , Imayavaramban Lakshmanan 1 , Prabin D. Majhi 1 , Lynette M. Smith 2 , Kay-Uwe Wagner 1,4 and Surinder K. Batra 1,3,4 1 Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA 2 Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE, USA 3 Department of Pathology, University of Nebraska Medical Center, Omaha, NE, USA 4 Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA * These authors contributed equally to this work Correspondence: Surinder K. Batra, email: // Keywords : Mucin 16 (MUC16), CA125, pancreatic cancer, JAK2, cancer stem cells Abbreviations : C-Ter, carboxy-terminal; CSC, cancer stem cell; SEA, sperm protein, enterokinase, agrin; JAK2, janus kinase 2 Received : December 13, 2014 Accepted : January 02, 2015 Published : January 21, 2015 Abstract MUC16 (CA125) is a type-I transmembrane glycoprotein that is up-regulated in multiple cancers including pancreatic cancer (PC). However, the existence and role of carboxyl-terminal MUC16 generated following its cleavage in PC is unknown. Our previous study using a systematic dual-epitope tagged domain deletion approach of carboxyl-terminal MUC16 has demonstrated the generation of a 17-kDa cleaved MUC16 (MUC16-Cter). Here, we demonstrate the functional significance of MUC16-Cter in PC using the dual-epitope tagged version (N-terminal FLAG- and C-terminal HA-tag) of 114 carboxyl-terminal residues of MUC16 (F114HA). In vitro analyses using F114HA transfected MiaPaCa-2 and T3M4 cells showed enhanced proliferation, motility and increased accumulation of cells in the G2/M phase with apoptosis resistance, a feature associated with cancer stem cells (CSCs). This was supported by enrichment of ALDH + CSCs along with enhanced drug-resistance. Mechanistically, we demonstrate a novel function of MUC16-Cter that promotes nuclear translocation of JAK2 resulting in phosphorylation of Histone-3 up-regulating stemness-specific genes LMO2 and NANOG. Jak2 dependence was demonstrated using Jak2 +/+ and Jak2 –/– cells. Using eGFP-Luciferase labeled cells, we demonstrate enhanced tumorigenic and metastatic potential of MUC16-Cter in vivo . Taken together, we demonstrate that MUC16-Cter mediated enrichment of CSCs is partly responsible for tumorigenic, metastatic and drug-resistant properties of PC cells.