The atypical ERK3 MAP kinase signaling pathway as a potential therapeutic target for metastatic breast and lung cancer

Metastatic cancer is the major cause of mortality amongst cancer patients, and treating metastatic cancer is currently a big challenge in the clinics. In addition to few available drugs, the metastatic lesions often develop acquired drug resistance. It is believed that interrupting the signaling pathways that are crucial for the progression of cancer disease, will increase the benefits of today’s cancer therapies.

Our research group has results indicating a regulatory role for ERK3, one of the atypical MAP kinases, in the invasion and migration potential of breast and lung cancer cells. In this project we aim to develop a kinase inhibitor drug(s) that will target ERK3 in the ERK3 MAP kinase signaling pathway in order to develop novel therapy targeted against metastatic breast and lung cancer.

Unravelling the mechanism(s) by which ERK3 regulates cancer cell invasion and migration is an important step in the development of a novel kinase inhibitor drug targeting ERK3. By knowing the detailed mechanisms, a specific and potent drug with few off-target hits and lesser toxicity can be designed. First, we want to determine if the atypical ERK3 MAP kinase signaling pathway could be a potential target in breast cancer therapy. Following this, we will further investigate the mechanisms in detail behind ERK3´s regulatory role in breast and lung cancer cell migration and invasion. Currently, we have results identifying ERK3 in a complex with key proteins important for cancer cell migration and invasion.

Image shows MDA-MB-231 triple negative breast cancer cells transfected with mCherry-ERK3 (left image) and a co-localization of mCherry-ERK3 with one of the key proteins (EGFP-tagged) identified in the complex with ERK3.