|Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2015: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
|Outline of Final Research Achievements
Membrane-associated protease inhibitors HAI-1 and -2 are important in regulating the pericellular serine protease activities of epithelial cells. This study aimed to analyze the roles for HAIs in normal homeostasis of epithelial cells and the effects of HAI insufficiency on cancer progression. We revealed that HAI-1 had suppressive roles in pericellular activations of HGF and PAR-2. HAI-1 was a suppressor of intestinal carcinogenesis and inhibited EMT, invasion, and metastasis of oral squamous cell carcinoma and pancreatic adenocarcinoma cells. Moreover, we found that HAI-1 maintained the assembly of keratin into desmosomes in keratinocytes by regulating PAR-2-dependent p38 signaling. Also, we have generated HAI-2floxed/floxed mouse that will be critically required for the development of the conditional HAI-1 knockout mouse. Those mice would accelerate the studies for in vivo functions of HAI-2.