Epigenetic Dysregulation of DNAJB6 Isoform Expression Contributes to Breast Cancer Invasion and Metastasis
NA methylation is a chemical modification on our DNA that defines healthy, normal expression of the genetic material, but in cancers, the distribution of this modification is drastically altered, in both quantity and location. While some such cancer-associated methylation changes can directly promote cancer formation and progression by turning on/off caretaker genes that normally prevent uncontrolled cell growth, our lab has discovered that other changes can impact which version of a caretaker gene is expressed in cancer. In particular, a gene named DnaJ heat shock protein family (Hsp40) member B6 (DNAJB6) has two versions whose expression levels can be dictated by DNA methylation. Previously, other scientists have shown that the longer version of DNAJB6 is often lost in aggressive breast cancer cells compared with benign cells or early stage cancer cells, without defining how such shift in expression might be achieved by the malignant cells. Although these prior reports suggest a cancer-suppressing role for the long version in breast cancer development, we are limited in what we can do with such information without knowing how the loss came about. Therefore, we propose to investigate if DNA methylation changes in aggressive breast cancer cells are directly responsible for the loss of DNAJB6 long version and to evaluate if targeting such abnormal DNA methylation can reverse the loss and in turn, inhibit aggressive cancer behaviors. We anticipate our studies to produce fundamental insights into the regulation of DNAJB6 in breast cancer and enable us to leverage this phenomenon for cancer intervention.
We are focusing on a gene that in the context of breast cancer, can change forms depending on the stage of the cancer. We believe that a chemical modification in our DNA, NA methylation, plays a role in switching the breast cancer form to an advantageous state. We are trying to study this phenomenon in the context of breast cancer to try and understand how changes in this modification can impact cancer.