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CD74-AKT Axis Is a Potential Therapeutic Target in Triple-Negative Breast Cancer

Jingchao Wang1, Daoyuan Huang1, Thu Anh Thai Nguyen2

  • 1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

Biology
|July 26, 2024
PubMed

Insights

Triple-negative breast cancer cells resist apoptosis. Targeting CD74 and AKT pathways can restore this process, offering a new strategy for TNBC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Triple-negative breast cancer (TNBC) exhibits resistance to apoptosis, a key mechanism for cancer cell death.
  • The role of CD74, a type II transmembrane protein, in cancer progression and chemoresistance is not fully understood.
  • Understanding the molecular mechanisms behind TNBC apoptosis resistance is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the role of CD74 in TNBC.
  • To elucidate the molecular mechanisms by which CD74 influences apoptosis resistance in TNBC.
  • To explore therapeutic strategies targeting the CD74 pathway for TNBC treatment.

Main Methods:

  • Gene expression analysis in cancer patients and patient-derived xenograft (PDX) models.
  • Assessment of CD74 expression correlation with cancer stem cell (CSC) and epithelial-mesenchymal transition (EMT) properties.
  • Investigation of the interaction between CD74, AKT signaling, and FAS-mediated apoptosis.
  • Evaluation of AKT inhibitors and CD74-derived peptides in restoring apoptosis.

Main Results:

  • CD74 is highly expressed in TNBC and correlates with CSC and EMT phenotypes.
  • AKT activation is critical for CD74 expression and stability, promoting oncogenic functions.
  • CD74 interacts with FAS, inhibiting FAS-mediated apoptosis.
  • Targeting the CD74/FAS and CD74-AKT axes synergistically restores apoptosis in TNBC cells.

Conclusions:

  • CD74 plays a significant role in promoting TNBC progression and apoptosis resistance.
  • The CD74/AKT axis is essential for maintaining CD74 expression and function in TNBC.
  • CD74 interferes with FAS-mediated apoptosis by directly binding to FAS.
  • Targeting the CD74/FAS and CD74-AKT pathways presents a promising therapeutic strategy for TNBC.
Keywords:
AKTCD74FAS (CD95)apoptosischemoresistancepeptidomimetic drugtriple-negative breast cancer (TNBC)

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