Role of GJA1-20k, a connexin 43 isoform, in survival and quiescence of prostatic cancer cells

Hello, my name is Aurélien Djian dit Zayan. I am actually working toward my Master's Degree in the university of Poitiers. During my presentation, I will talk about my internship in the 4CS laboratory of Poitiers. During this internship, I will work in collaboration with Mr. Monvoisin and Mr. Cronier on the role of GJA1-20k in survival and the quiescence of prostatic cancer cells.

 

Prostatic cancer is the most common cancer in men and around 50,000 new cases are detected each year in France. Metastases due to prostate tumor cells can reoccur several months or years after the initial diagnosis and treatment. This occurs after a period of cellular quiescence of cancerous cells. Understanding the mechanisms responsible for this cellular quiescence shows important implications in diagnostic and therapy. Over the past 50 years, increasing experimental evidences have established that connexins (Cxs) and gap junctional intercellular communication (GJIC) ensure an important role in both the onset and development of cancerous processes. In vitro and In vivo experiments show connexin 43 (Cx43) increasing the aggressiveness of tumor cells when it is over-expressed in the plasma membrane.

 

Recently, the 4CS laboratory identified a short isoform of Connexin 43 called GJA1-20k. Contrary to the full connexin 43, its increased expression in human prostate cancer cells leads to a significant reduction in the dynamics of tumor cells such as migration and invasion. In regard to this discovery, my internship will focus on the study of the role of GJA1-20k on cellular quiescence by addressing its potential action in the response to hypoxic stress conditions or oxidative one. Moreover, I will also study the mTOR signaling pathway, known to inhibit the expression of GJA1-20k and whose activity is inhibited in hypoxic conditions.