Targeting MCM2 function as a novel strategy for the treatment of highly malignant breast tumors

Area of Science:

• Oncology
• Molecular Biology
• Cancer Therapeutics

Background:

• Highly malignant tumors exhibit elevated minichromosome maintenance 2 (MCM2) protein levels, correlating with advanced stage and poor prognosis.
• Previous research demonstrated Friend leukemia virus (FLV) envelope protein gp70 binding to MCM2, inhibiting nuclear translocation and promoting apoptosis in infected cells.

Purpose of the Study:

• To investigate MCM2 expression in clinical breast cancer samples, particularly triple-negative breast cancer (TNBC) and cancer stem cell (CSC) populations.
• To develop and evaluate a novel therapeutic strategy targeting MCM2 in breast cancer using a protein transduction domain (PTD) conjugated to gp70.

Main Methods:

• MCM2 expression was assessed in clinical breast cancer samples and CSC marker-positive cells.
• The Hph-1 protein transduction domain was conjugated to gp70 (Hph-1-gp70) to facilitate cytoplasmic delivery into murine breast cancer cells with high MCM2 expression.
• The efficacy of Hph-1-gp70 in inducing DNA damage and apoptosis was evaluated both in vitro and in vivo.

Main Results:

• MCM2 was found to be highly expressed in invasive breast carcinoma, with notable levels in TNBC and CSC-like cells.
• Hph-1-gp70 was successfully delivered into the cytoplasm of target breast cancer cells.
• The treatment with Hph-1-gp70 significantly enhanced DNA damage-induced apoptosis in cancer cells, both in vitro and in vivo.

Conclusions:

• MCM2 is a relevant therapeutic target in highly malignant breast cancers, including TNBC.
• The Hph-1-gp70 conjugate demonstrates potential as a novel therapeutic agent for inducing apoptosis in MCM2-expressing breast cancer cells and CSCs.
• This MCM2-targeted strategy holds promise for improving treatment outcomes in aggressive breast cancer subtypes and eradicating CSC-like cells.