c-Kit Induces Migration of Triple-Negative Breast Cancer Cells and Is a Promising Target for Tyrosine Kinase...

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Triple-negative breast cancer (TNBC) presents a poor prognosis due to limited targeted therapy options.
• c-Kit, a receptor tyrosine kinase (RTK), is a potential molecular target for novel anticancer drug development.
• The role of c-Kit in TNBC remains underexplored, necessitating further investigation into its expression, function, and therapeutic implications.

Purpose of the Study:

• To investigate the expression and functional role of c-Kit in TNBC.
• To evaluate the efficacy of c-Kit targeting tyrosine kinase inhibitors (TKIs) in TNBC models.
• To explore Nilotinib as a potential therapeutic agent for TNBC.

Main Methods:

• In vitro analysis of c-Kit expression and signaling pathways (STAT3, Akt, ERK1/2) in TNBC cell lines.
• In silico analysis of c-Kit expression in public TNBC patient datasets.
• Assessment of TNBC cell response to TKIs, including Nilotinib and Doxorubicin.

Main Results:

• Functional c-Kit was detected on the cell membrane of TNBC cells.
• c-Kit stimulation activated STAT3, Akt, and ERK1/2, enhancing cell migration but not proliferation or Doxorubicin response.
• c-Kit expression in tumors did not correlate with patient survival.
• TNBC cells demonstrated susceptibility to TKIs, with Nilotinib showing greater efficacy than Doxorubicin.

Conclusions:

• TNBC cells express functional c-Kit, identifying it as a targetable molecule.
• Nilotinib exhibits significant efficacy against TNBC cells, positioning it as a potential candidate drug for TNBC treatment.
• Targeting c-Kit with TKIs like Nilotinib offers a promising therapeutic strategy for TNBC.