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Unraveling Connective Tissue Growth Factor as a Therapeutic Target and Assessing Kahweol as a Potential Drug

Jeong Hee Lee1, Jongsu Kim1, Hong Sook Kim1

  • 1Department of Biological Sciences, Sungkyunkwan University, Suwon 16419, Republic of Korea.

International Journal of Molecular Sciences
|November 25, 2023
PubMed

Insights

Connective tissue growth factor (CTGF) shows prognostic value in triple-negative breast cancer (TNBC). Kahweol, a coffee compound, suppresses TNBC cell motility by downregulating CTGF, offering a potential new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Triple-negative breast cancer (TNBC) presents aggressive behavior and limited therapeutic strategies.
  • Identifying novel prognostic markers and therapeutic targets is crucial for improving TNBC patient outcomes.
  • Connective tissue growth factor (CTGF) has emerged as a molecule of interest in cancer progression.

Purpose of the Study:

  • To evaluate the clinical significance of CTGF as a prognostic marker in TNBC.
  • To investigate the therapeutic potential of kahweol, a coffee diterpene, in TNBC treatment.
  • To elucidate the molecular mechanisms underlying CTGF's role and kahweol's effects on TNBC cell motility.

Main Methods:

  • Survival analysis using The Cancer Genome Atlas (TCGA) database for CTGF prognostic significance in breast cancer subtypes.
  • Functional annotation and gene set enrichment analyses to understand CTGF's role in migratory pathways.
  • In vitro studies using MDA-MB 231 TNBC cells to assess the effects of recombinant CTGF (rCTGF) and CTGF knockdown (siRNA) on cell motility.
  • Molecular analysis of signaling pathways (ERK, P38, PI3K/AKT, FAK) affected by kahweol treatment.

Main Results:

  • CTGF demonstrated significant prognostic effects specifically in TNBC patients.
  • CTGF was implicated in pathways regulating cell migration, a key feature of TNBC.
  • rCTGF enhanced TNBC cell motility, while CTGF knockdown reduced it.
  • Kahweol treatment decreased TNBC cell motility and downregulated CTGF expression and associated signaling molecules (p-ERK, p-P38, p-PI3K/AKT, p-FAK).
  • Kahweol's motility-reducing effects were mediated through CTGF, as rCTGF could restore motility in kahweol-treated cells.

Conclusions:

  • CTGF serves as a potential prognostic biomarker for guiding TNBC treatment strategies.
  • Kahweol exhibits promising antitumor activity in TNBC by suppressing cell motility via CTGF regulation.
  • These findings support the development of targeted therapies involving CTGF modulation for improved TNBC clinical outcomes.
Keywords:
connective tissue growth factor (CTGF)kahweoltriple-negative breast cancer (TNBC)

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