The role of ERK5 in HER2+ breast cancer

UoM administered thesis: Phd

  • Authors:
  • Jingwei Zhang

Abstract

In the first part of my phd work, I deciphered ERK5 as a new potential target to overcome resistance to anti-HER2 target therapy (small molecular kinase inhibitor and monoclonal antibody) in HER2+ breast cancer. More specifically, I found that ERK5 is constitutively activated in HER2+ breast cancer cells, and this constitutive activation can be inhibited by lapatinib in anti-Her2 sensitive cells but not in resistant cells. I also validated that ERK5 inhibitors (JWG-045 and AX15836) and MEK5 inhibitor (BIX02189) suppressed Rb phosphorylation in HER2+ breast cancer cells. As a result, inhibition of MEK5/ERK5 signalling enhanced anti-HER2 therapy in resistant breast cancer cell lines by causing G1 arrest. Additionally, I found that shERK5 enhanced the anti-lapatinib effect in Xenograft model. In the second part of my phd work, I found that ERK5 phosphorylation was transiently increased by irradiation in HER2+ breast cancer cells. Also, this transient activation of ERK5 was involved in IR-induced G2/M arrest in HER2+ breast cancer cells.

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Original languageEnglish
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Award date1 Aug 2022