Researchers demonstrate potential role of Gli1 protein in anoikis resistance
July 27, 2012 — Research at the Texas Tech University Health Sciences Center (TTUHSC) has revealed important characteristics associated with certain types of cancer cells that may lead to new ways to treat some ovarian cancer tumors. The findings were recently published in The Journal of Biological Chemistry.
Diindolylmethane mediated Gli1 Suppression Induces Anoikis in Ovarian Cancer cells in vitro and blocks tumor formation ability in vivo
Background: Anoikis, a detachment free cell death and pathways involving anoikis were not well understood.
Results: Diindolylmethane and cyclopamine induce anoikis in vitro and in vivo by inhibiting Gli1.
Conclusion: Gli1 suppresses anoikis resistance and inhibits tumor formation ability of ovarian cancer cells.
Significance: This is the first report demonstrating the role of Gli1 in anoikis. Gli1 inhibitors can be used clinically to inhibit metastasis.
The research was conducted by Sanjay K. Srivastava, Ph.D., a professor of cancer biology for the Department of Biomedical Sciences at the TTUHSC School of Pharmacy in Amarillo. Funding was provided in part by the National Cancer Institute at the National Institutes of Health.
Tumor metastasis is an important hallmark of cancer and cells need to detach from the extracellular matrix (ECM) to metastasize. ECM is the defining feature of the body’s connective tissue. During the detachment process, cells undergo stress and die in a process called anoikis. However, cells that are resistant to this form of cell death metastasize to different organs.
In their research, Srivastava and his graduate student, Prabodh Kandala, demonstrated for the first time the potential role the Gli1 protein can play in anoikis resistance. Gli1 is aberrantly expressed in ovarian tumors.
By treating different ovarian cancer cells with diindolylmethane (DIM) or cyclopamine, Srivastava’s team was able to decrease the expression of the Gli1 protein and reduce anoikis resistance. DIM is an active ingredient of cruciferous vegetables such as cauliflower, cabbage, cress, bok choy, broccoli and similar green leafy vegetables. The study also demonstrated that DIM or cyclopamine treatment significantly reduced the tumor formation in mice.
Press release courtesy of the Texas Tech University Health Sciences Center. Photo courtesy of Wikipedia.