In conversation with first author, Sakhi Goel.
Transcriptional network involving ERG and AR orchestrates Distal-less homeobox-1 mediated prostate cancer progression.
Goel S, Bhatia V, Kundu S, Biswas T, Carskadon S, Gupta N, Asim M, Morrissey C, Palanisamy N, Ateeq B.
Nature communications. 2021 Sep 7;12(1):1-22.
Congratulations Sakshi to you and all authors for this wonderful study. What is the major gap in understanding of Prostate cancer that your study addresses?
Sakshi Goel: Distal-less homeobox-1 (DLX1) is widely recognized as a biomarker which is used to detect prostate cancer (PCa) owing to its higher expression in PCa patients. But the major gap existed that how the level of DLX1 is increased in PCa and what role does it play. Our study addressed these two important questions and established the role of DLX1 in promoting cancer growth and it’s spread to other organs. We also identified the role of well-known PCa promoting proteins AR and ERG in regulating DLX1. Further we demonstrate the treatment strategies which could help in reducing DLX1 expression, thereby regressing the tumor growth.
What was the most challenging part of the study?
Sakshi Goel: DLX1 is a homeobox gene which is known to play important role in development of jaws, neurons, and bone. It is not known to play any role during the development of prostate gland and hence is not expressed there. Additionally, not much was known about the role of DLX1 in PCa. Thus, the most challenging part was to identify the mechanism of DLX1 upregulation and its functional significance in the cancer type of an unrelated organ.
Where do you see the application of this study, particularly in the Indian context?
Sakshi Goel: Our study has identified that DLX1 and its tumor promoting ability can be targeted with the use of Bromodomain and extraterminal protein inhibitors either alone or coupled with the drugs against androgen receptor signaling. There are several commercially available urine-based diagnostics tests for detecting DLX1 levels in PCa patients. In western countries, these kits are used to detect PCa. If the DLX1 diagnostic test is utilized in India as well, the disease could be identified at the early stage, and it would be relatively easy to categorize PCa patients with higher DLX1 levels. This would further assist to predict the patients who could respond to suggested treatment strategy. Hence, the present study would be immensely helpful for better disease management of PCa patients with higher DLX1 levels.
How did the collaboration with other research group help?
Sakshi: The collaborations with other research groups provide a broader perspective to the study. Additionally, it helps in widening the biological tools to validate the findings thus providing a significant contribution in the research. In the present study our collaborations gave us access to the larger cohorts of both primary and advanced stage PCa patients. Using which we were able to identify that ~60% of PCa patients shows higher expression of DLX1. Further, we also validated the positive association between AR, ERG and DLX1 in the PCa patient samples.
