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| Research: Sakurai-Yageta Mika Ph.D. |
Analysis of the mechanisms that CADM1 plays a role in tumor suppression in epithelial cells and in cell invasion in ATL cells
Background and Objects
Cell-cell interaction is important not only for physical interaction of cells but also for the regulations of cell growth and motility. CADM1 (cell adhesion molecule 1) is a cell-cell adhesion molecules belonging to immunoglobulin superfamily which we identified as a tumor suppressor in non-small cell lung cancer (NSCLC). CADM1 is also called IgSF4A, RA175, sgIGSF, SynCAM and Necl2 by different research groups. Expression of CADM1 is lost or reduced in various cancer derived from epithelial tissues, including NSCLC, renal cancer, breast cancer, and pancreatic cancer. In normal epithelial cells, CADM1 is involved in the formation and the maintenance of cell-cell adhesion, and suppresses tumor formation and progression. These findings suggest that CADM1 plays a role as a tumor suppressor in these cancer cells. In contrast, in adult T-cell leukemia (ATL) cells, CADM1 is ectopically expressed, and appears to promote the interaction of ATL cells with endothelial cells during extravasation which is the initial step of cell invasion.
Thus, CADM1 has two reciprocal roles in tumorigenesis; a tumor suppression
in epithelial tumors and cell invasion in ATL. However, precise mechanisms
of the regulation are still unknown. Therefore, I am investigating the
following research projects with several graduate students;
1) Analysis of the mechanism of cell-cell adhesion and cell invasion mediated by CADM1 using live-cell imaging
2) Analyses of the upstream regulations of CADM1 by biochemical and cell biological approaches
Projects
1) Analysis of the spatio-temporal dynamics of CADM1 and related molecules
- CADM1 dynamics in epithelial cells during the formation and maintenance
of cell-cell adhesion
- CADM1 dynamics during trans-endothelial migration (TEM) of ATL cells
- Effect of CADM1 on the dynamics of receptor tyrosine kinases
2) Analyses of the mechanisms that regulate CADM1 expression and modification
- miRNA-mediated regulations of CADM1 expression and its role in tumorigenesis
- Post-translational modification of CADM1 through glycosylation in epithelial
and ATL cells, and its role in tumorigenesis
- Shedding of CADM1 at the extracellular and intracellular domain, and
its role in cell motility and cell death
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Recent publications
1. Nagata M, Sakurai-Yageta M, Yamada D, Goto A, Ito A, Fukuhara H, Kume H, Morikawa T, Fukayama M,
Homma Y, Murakami Y. Aberrations of a cell adhesion molecule CADM4 in renal
clear cell carcinoma. Int J Cancer, in press.
2. Sakurai-Yageta M, Masuda M, Tsuboi Y, Ito A, Murakami Y. Tumor suppressor CADM1 is involved
in epithelial cell structure. Biochem Biophys Res Commun. 2009, 390:977-82.
3 Sakurai-Yageta M, Recchi C, Le Dez G, Sibarita JB, Daviet L, Camonis J, D’Souza-Schorey C, Chavrier, P. The interaction of IQGAP1 with the exocyst complex is required for tumor cell invasion downstream of Cdc42 and RhoA. J Cell Biol. 2008, 181:985-998.
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