title: Novel roles for LIX1L in promoting cancer cell proliferation through ROS1-mediated LIX1L phosphorylation.
abstract: Herein, we report the characterization of Limb expression 1-like, (LIX1L), a putative RNA-binding protein (RBP) containing a double-stranded RNA binding motif, which is highly expressed in various cancer tissues. Analysis of MALDI-TOF/TOF mass spectrometry and RNA immunoprecipitation-sequencing of interacting proteins and the microRNAs (miRNAs) bound to LIX1L revealed that LIX1L interacts with proteins (RIOK1, nucleolin and PABPC4) and miRNAs (has-miRNA-520a-5p, -300, -216b, -326, -190a, -548b-3p, -7-5p and -1296) in HEK-293 cells. Moreover, the reduction of phosphorylated Tyr(136) (pTyr(136)) in LIX1L through the homeodomain peptide, PY136, inhibited LIX1L-induced cell proliferation in vitro, and PY136 inhibited MKN45 cell proliferation in vivo. We also determined the miRNA-targeted genes and showed that was apoptosis induced through the reduction of pTyr(136). Moreover, ROS1, HCK, ABL1, ABL2, JAK3, LCK and TYR03 were identified as candidate kinases responsible for the phosphorylation of Tyr(136) of LIX1L. These data provide novel insights into the biological significance of LIX1L, suggesting that this protein might be an RBP, with implications for therapeutic approaches for targeting LIX1L in LIX1L-expressing cancer cells.
authors: Department of Tumor Pathology, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors: Satoki
authors: S
authors: Nakamura
authors: Department of Tumor Pathology, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors: Tomoaki
authors: T
authors: Kahyo
authors: Department of Tumor Pathology, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors: Hong
authors: H
authors: Tao
authors: Equipment Center, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors: Kiyoshi
authors: K
authors: Shibata
authors: Department of Tumor Pathology, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors: Nobuya
authors: N
authors: Kurabe
authors: Department of Tumor Pathology, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors: Hidetaka
authors: H
authors: Yamada
authors: Department of Tumor Pathology, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors: Kazuya
authors: K
authors: Shinmura
authors: Cancer Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors: Kazunori
authors: K
authors: Ohnishi
authors: Department of Tumor Pathology, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors: Haruhiko
authors: H
authors: Sugimura
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015180:Electrophoresis, Gel, Two-Dimensional; D057075:Enzyme Assays; D055785:Gene Knockdown Techniques; D059014:High-Throughput Nucleotide Sequencing; D007150:Immunohistochemistry; D013058:Mass Spectrometry; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D040901:Proteomics; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012984:Software; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D051339:Actin Depolymerizing Factors; D000970:Antineoplastic Agents; C000610666:LIX1L protein, human; D035683:MicroRNAs; D010455:Peptides; D011518:Proto-Oncogene Proteins; D016601:RNA-Binding Proteins; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human