Characterization and use of CCN proteins in suppressing colorectal cancers
| Autor: | Hung-Yi Chang, 張宏毅 |
|---|---|
| Rok vydání: | 2012 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 100 The matricellular CCN5, a secreted matrix-associated molecule, belongs to the CCN protein family. Studies have shown that CCN5 is involved in breast cancer tumorigenesis that it can modulate multiple cellular functions, including cell migration, adhesion, invasion, metastasis and EMT process. The available clinical data show that CCN5 expression levels are inversely correlated with malignancy stage of human colorectal cancers, which implying that CCN5 may function as a tumor suppressor. However, the molecular mechanism underlying CCN5-induced colorectal cancer suppression is largely unknown. The present study is to investigate the role of CCN5 in colorectal tumorigenesis. We found that CCN5 expression was nearly undetectable in all tested colorectal cancer cell lines. By the baculovirus expression system, we have successfully generated and purified the recombinant CCN5 proteins for functional characterizations. Upon addition of exogenous CCN5 proteins, cellular mobility was inhibited in HCT116 as well as SW480 cells. Along with retardation of cell migration, CCN5-treated cells were converted from malignant morphology into cobblestone-like shapes, with loss of lamelipodia and actin stress fiber formation. Consistent results were also obtained by lentiviral overexpression of CCN5 gene in the cancer cells. Moreover, we have found that cancer sphere formation was impaired upon CCN5 treatment. This indicates that CCN5 may be also involved in the control of colorectal cancer stemness. Taken together, our data support the guardian role of CCN5 in suppressing colorectal cancers. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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