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Updated: Feb 18, 2026

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
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PTK6 regulates growth and survival of endocrine therapy-resistant ER+ breast cancer cells

Koichi Ito1, Sun Hee Park1, Igor Katsyv2

  • 1Division of Hematology and Medical Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, 1468 Madison Ave, New York, NY USA.

NPJ Breast Cancer
|November 24, 2017
PubMed

Insights

The non-receptor tyrosine kinase PTK6 drives growth in estrogen receptor-positive (ER+) breast cancer, even with resistance to therapies. Inhibiting PTK6 induces cancer cell death and halts tumor growth, suggesting PTK6 as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • PTK6/BRK, a non-receptor tyrosine kinase, is upregulated in various cancers, including breast, prostate, and ovarian.
  • PTK6 plays a role in oncogenic phenotypes like proliferation, migration, and survival, and its inhibition can overcome HER2+ breast cancer resistance.
  • The function of PTK6 in ER+ Luminal breast cancer, despite its high expression, remains largely uncharacterized.

Purpose of the Study:

  • To investigate the role of PTK6 in ER+ Luminal breast cancer cells.
  • To determine the effect of PTK6 modulation on the growth and survival of ER+ breast cancer cells, including those resistant to endocrine therapies.
  • To elucidate the molecular mechanisms underlying PTK6's function in ER+ breast cancer.

Main Methods:

  • Investigated PTK6 function in ER+ Luminal breast cancer cell lines.
  • Assessed the impact of PTK6 overexpression and downregulation on cell proliferation, apoptosis (cleaved PARP, AnnexinV+), and 3D Matrigel cultures.
  • Utilized MCF-7 xenograft models to evaluate PTK6's effect on primary tumor growth in tamoxifen-sensitive and resistant contexts.
  • Examined the role of p38 MAPK activation in PTK6 downregulation-induced apoptosis.

Main Results:

  • Enhanced PTK6 expression promoted ER+ breast cancer cell growth, including tamoxifen-treated cells.
  • PTK6 downregulation induced apoptosis and impaired growth in ER+ breast cancer cells, including those resistant to tamoxifen, fulvestrant, and estrogen deprivation.
  • PTK6 downregulation abrogated primary tumor growth in both tamoxifen-sensitive and resistant MCF-7 xenografts.
  • p38 MAPK activation was identified as critical for PTK6 downregulation-induced apoptosis.

Conclusions:

  • PTK6 plays a critical role in the growth and survival of ER+ Luminal breast cancers.
  • PTK6 downregulation effectively inhibits tumor growth and induces apoptosis in ER+ breast cancer models, including resistant subtypes.
  • PTK6 represents a promising therapeutic target for ER+ breast cancers, with conserved survival regulation mechanisms across breast cancer subtypes.

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