@phdthesis{oai:oist.repo.nii.ac.jp:00002005,
 author = {Burriel, Sandrine},
 month = {2021-04-05, 2021-04-05},
 note = {The function of the lemur tail kinase (LMTK) family in health and disease remainslargely unknown. LMTK1 has two isoforms, LMTK1B (transmembrane) and LMTK1A(cytosolic), predominantly expressed in neurons where its kinase activity regulates axonand dendrite formation. LMTK1 can also act as a scaffold protein, recruiting proteinphosphatase 1 (PP1) and SPAK to regulate the activity of the NKCC1 cotransporter.Recent   work   established   that   LMTK1   downregulation   can   contribute   to   cancerprogression.  In this project, we investigated the kinase activity of LMTK1A in lungcancer. We verified predominant expression of the LMTK1A variant in healthy lungtissue.   Analysis   of   patient   data   from   The   Cancer   Genome   Atlas   confirmed   LMTK1mRNA downregulation in non-small cell lung cancer tumors, moderately affecting thesurvival   of   lung   adenocarcinoma   (LUAD)   patients.   In   A549   cells,   restoring   stableLMTK1 expression reduces cell proliferation, while in NCI-H441 cells, siRNA knock-down of  LMTK1  increases  cell  proliferation.  Stable expression of  mutant  versions ofLMTK1   identified   the   kinase   activity   as   the   main   driver   of   this   effect.   Cell   cycleanalysis demonstrated that LMTK1A expression slows progression from G1 to S phase,decreasing Cyclin E1 and E2F1 expression. Immunofluorescence showed that wild-typeLMTK1A expression dramatically delayed cell cycle-regulated nuclear translocation ofYAP. These effects were abrogated by the kinase-negative LMTK1A mutant. Finally,we   identified   a   direct   interaction   between   LMTK1A   and   the   tumor   suppressorMerlin/NF2, a known regulator of the Hippo pathway. We hypothesise a novel role forLMTK1A kinase activity as a regulator of the Hippo pathway.},
 school = {Okinawa Institute of Science and Technology Graduate University},
 title = {肺腺癌におけるLMTK1の機能的解析},
 year = {}
}