| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Morphological transformation is a fundamental feature of malignant cancer cells. The tumor suppressor, TSLC1/IGSF4, is involved in cell adhesion and preferentially inactivated in invasive cancer. We have previously shown that TSLC1 associates with an actin-binding protein, DAL-1/4.1B, and a scaffold protein, membrane protein palmitoylated 3(MPP3). Here, we identified MPP1/p55 and MPP2/DLG2 as additional cytoplasmic proteins binding to TSLC1 and investigated the roles of the TSLC1 cascade in epithelial cell morphology and its malignant transformation. MPP1, MPP2, and MPP3 interacted directly with DAL-1, forming a tripartite complex with TSLC1. Whereas these complexes localized along the cell membranes in confluent HEK293 cells, only MPP2, but not MPP1 or MPP3, was recruited to the TSLC1-DAL-1 complex in the early process of cell adhesion. When the TSLC1 function was abrogated by RNAi, HEK293 losed epithelial-like structure and showed flat morphology with immature cell adhesion. Furthermore, DAL-1 and MPP2, as well as E-cadherin and ZO-1, were mislocalized from the membrane. Loss of TSLC1 was also correlated with the transformed phenotype of lung cancer cells. These findings suggest that TSLC1 is involved in the formation of epithelial-like cell structure with DAL-1 and MPPs, while loss of its function could cause morphological transformation of cancer cells.
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