Cancer Biology – Tumor Suppression

We are interested in a new are of cancer biology, tumor suppression by the recently discovered CLCA family of calcium-activated chloride channel regulators.  We have isolated several members of this gene family from mouse and human and characterized their expression in normal and cancer cells.  We find that in normal breast, the CLCA2 gene is strongly induced by  master regulator p53 in response to multiple physiological stresses encountered by the evolving tumor cell, including cell detachment and DNA damage by chemotherapeutic agents.  On the other hand, in breast cancer cells, the gene is downregulated, suggesting a role as a tumor suppressor.  Accordingly, we find that cancer cells forced to express CLCA2 die by apoptosis, while normal cells cease dividing.  We have established collaborations with multiple groups at SIU to investigate the role of CLCA2 in tumorigenesis, metastasis and normal development.  In addition, we recently received funding from NCI to test the therapeutic potential of CLCA2 in cancer.  In the longer term, and beyond the role of CLCAs in tumorigenesis, we are probing the structure and function of this mysterious family of proteins using the tools of molecular biology, genetics, genomics/proteomics, electrophysiology, biochemistry and cell biology.

Recent Publications

Yu Y, Ramena G, and Elble RC. 2011. The role of cancer stem cells in relapse of solid tumors. Frontiers in Biosciences, in press.

Walia V, Yang Y, Cao D, Cheng J, Rao K, Hollier B, Mani S, Sun M., Premkumar L, and Elble RC.  2011. Loss of breast epithelial marker hCLCA2 promotes epithelial to mesenchymal transition and metastasis. Oncogene, in press.

Walia V, Kakar S, and Elble RC. 2011. Micromanagement of mitochondrial apoptosis by p53. Frontiers in Biosciences 16:749-758.

Recent Presentations

Yang Yu, Vijay Walia, Miao Sun, and Randolph Elble.  Loss of hCLCA2 Promotes Epithelial to Mesenchymal Transition in Breast Cancer.  AACR Annual Meeting, Orlando, FL, April 1-4, 2011.

Yu Y and Elble R.  Biotherapy of triple-negative breast cancer with a secreted tumor suppressor.  Breast Cancer ERA of Hope Meeting, Orlando, FL, August 2, 2011.

Yu Y, Johnson S, and Elble R.  Prospecting the venom of a predatory neotropical ant for anti-cancer drugs.  Breast Cancer ERA of Hope Meeting, Orlando, FL, August 2, 2011.

Ramena G, Walia V, Yu Y, Elble R.  A novel biotherapeutic for triple-negative breast cancer.  SIU Trainee Symposium, Springfield, IL, May 2011.

Yu Y, Walia V, Sun M, and Elble R.  Loss of hCLCA2 promotes epithelial to mesenchymal transition in breast cancer.  SIU Trainee Symposium, Springfield, IL, May 2011.