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Updated: Jan 26, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

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Leukemia Inhibitory Factor Promotes Castration-resistant Prostate Cancer and Neuroendocrine Differentiation by

Yen-Nien Liu1,2,3, Shaoxi Niu4, Wei-Yu Chen5,6

  • 1Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. liuy@tmu.edu.tw xzhang@tjh.tjmu.edu.cn jiaoti.huang@duke.edu.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|April 10, 2019
PubMed
Abstract

Insights

Leukemia inhibitory factor (LIF) promotes castration-resistant prostate cancer (CRPC) and neuroendocrine differentiation following androgen deprivation therapy (ADT). Targeting the ZBTB46-LIF pathway may inhibit CRPC progression and serve as a diagnostic biomarker.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Castration-resistant prostate cancer (CRPC) presents therapeutic challenges due to unknown molecular targets and recurrence.
  • Therapeutic resistance in CRPC is linked to neuroendocrine differentiation and androgen-responsive pathway dysregulation.

Purpose of the Study:

  • To investigate regulatory mechanisms driving therapeutic resistance in prostate cancer.
  • To identify effectors of the oncogenic network promoting neuroendocrine differentiation and resistance.

Main Methods:

  • Assessed prostate adenocarcinoma and CRPC samples using immunohistochemistry (IHC) and other assays.
  • Evaluated intracellular mechanisms sustaining neuroendocrine differentiation and therapeutic resistance.

Main Results:

  • Leukemia inhibitory factor (LIF) is induced by androgen deprivation therapy (ADT) and upregulated by ZBTB46, promoting CRPC and neuroendocrine differentiation.
  • High ZBTB46 expression activates LIF-STAT3 signaling, inducing neuroendocrine features; LIF abundance is mediated by ZBTB46 binding to the LIF regulatory sequence.
  • Elevated serum LIF titers correlate with higher tumor grade and metastatic prostate cancer.

Conclusions:

  • LIF is a potential serum biomarker for advanced prostate cancer diagnosis.
  • Targeting the ZBTB46-LIF axis may inhibit CRPC development and neuroendocrine differentiation post-ADT.

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