BEGIN:VCALENDAR VERSION:2.0 PRODID:researchseminars.org CALSCALE:GREGORIAN X-WR-CALNAME:researchseminars.org BEGIN:VEVENT SUMMARY:Prof. Dr. Tony Hunter (Salk Institute for Biological Studies) DTSTART:20210120T040000Z DTEND:20210120T050000Z DTSTAMP:20260423T024725Z UID:MCB_LUMS/11 DESCRIPTION:Title: New Signal Transduction Targets for Cancer Therapy\nby Prof. Dr. Ton y Hunter (Salk Institute for Biological Studies) as part of Colloquium zoo ming Molecular & Cellular Biology LUMS\n\n\nAbstract\nPancreatic ductal ad enocarcinoma (PDAC) has a dismal prognosis with few treatment options. We have identified leukemia inhibitory factor (LIF)\, a stem cell factor\, as a key paracrine factor\, secreted mainly by activated cancer-associated-f ibroblasts (CAFs) in the tumor micro-environment (TME)\, that acts on panc reatic tumor cells to maintain a stem cell-like population. Blockade of LI F with a neutralizing monoclonal antibody (mAb) slows tumor progression in the KPC mouse model of PDAC and augments efficacy of gemcitabine chemothe rapy treatment to prolong survival. LIF levels are strongly elevated in bo th mouse and human pancreatic tumor tissue\, and LIF is also is detected i n serum from tumor-bearing mice and human PDAC patients\, suggesting its u se as both as a biomarker and as a therapeutic target. In addition its act ion on tumor cells\, we have found that LIF acts on myeloid cells in the i mmune microenvironment to sustain a protumorigenic population of tumor-ass ociated macrophages.\n\n \n\nHistidine phosphorylation\, the so-called “ hidden phosphoproteome”\, is poorly characterized. To study histidine ph osphorylation we generated mAbs that selectively recognize the 1-pHis and 3-pHis-isoforms\, and have determined the structural basis of antibody rec ognition of pHis. We have used these mAbs for immunoblotting and immunoflu orescence staining to detect increased levels of pHis proteins in human ce ll lines\, and also to survey the pHis proteome and identify new sites of histidine phosphorylation. Using these mAbs\, we collaborated with Michael Hall (Biozentrum\, Basel) to show that pHis levels are elevated in liver tumors in a mouse model\, and in human hepatocellular carcinoma (HCC) tumo r tissue\, as a result of reduced levels of the LHPP pHis phosphatase in t umor tissue. On this basis\, we propose that LHPP serves as a tumor suppre ssor in HCC\, and that histidine phosphorylation can act as a cancer drive r. Consistently\, we have recently observed elevated levels of pHis protei ns in PDAC stromal cells.\n LOCATION:https://researchseminars.org/talk/MCB_LUMS/11/ END:VEVENT END:VCALENDAR