Association of a lung tumor suppressor TSLC1 with MPP3, a human homologue of Drosophila tumor suppressor Dlg

Hiroshi Fukuhara, Mari Masvuda, Mika Yageta, Takeshi Fukami, Masami Kuramochi, Tomoko Maruyama, Tadaichi Kitamura, Yoshinori Murakami

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)

Abstract

We have previously identified the tumor suppressor in lung cancer 1 (TSLC1) gene as a novel tumor suppressor in human non-small cell lung cancer (NSCLC) by functional complementation. TSLC1 encodes a membrane glycoprotein belonging to an immunoglobulin superfamily and participates in cell adhesion. A truncating mutation of the TSLC1 corresponding to its cytoplasmic domain in a primary NSCLC tumor suggests that this domain is important for tumor suppressor activity. Here, we report that TSLC1 directly associates with MPP3, one of the human homologues of a Drosophila tumor suppressor gene, Discs large (Dlg). This interaction was dependent on the presence of a PDZ-binding motif at the carboxyl terminus of TSLC1. Furthermore, TSLC1 and MPP3 were colocalized at the cell-cell attachment sites in both a low and a high cell density. The MPP3 gene was expressed in normal lung as well as in many tissues examined except for peripheral blood lymphocytes but lost its expression in one of the nine NSCLC cell lines. These results suggest that TSLC1 and MPP3 are involved in the same cascade of cell-cell interaction, and that the disruption of this cascade might lead cells to malignant growth and tumor formation in lung cancer.

Original languageEnglish
Pages (from-to)6160-6165
Number of pages6
JournalOncogene
Volume22
Issue number40
DOIs
Publication statusPublished - 2003 Sep 18

Keywords

  • Discs large
  • Lung cancer
  • MPP3
  • TSLC1
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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