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Fibroblast growth factor-inducible 14 regulates cell growth and multidrug resistance of small-cell lung cancer

Xiaoping Li1, Weiliang Zhu, Zhenzhu Chen

  • 1Departments of aPathology bOncology, Zhujiang Hospital, NanFang Medical University cDepartment of Organ Transplantation, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.

Anti-Cancer Drugs
|July 24, 2014
PubMed

Insights

Fibroblast growth factor-inducible 14 (Fn14) promotes small-cell lung cancer (SCLC) growth and chemoresistance by upregulating Bcl-xl via the NF-κB pathway. Targeting Fn14 may offer new therapeutic strategies for SCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Fibroblast growth factor-inducible 14 (Fn14) is implicated as an oncogene in various cancers.
  • The role of Fn14 in small-cell lung cancer (SCLC) remains largely unexplored.
  • Understanding Fn14's function in SCLC is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the biological functions of Fn14 in SCLC cell growth and chemoresistance.
  • To elucidate the molecular mechanisms underlying Fn14's effects in SCLC.
  • To assess Fn14 as a potential therapeutic target for SCLC.

Main Methods:

  • Immunohistochemistry was used to examine Fn14 expression in 51 SCLC tissue samples.
  • Fn14 was overexpressed or knocked down in SCLC cell lines (H69, H446, H69AR, H446AR) to study its impact on cell growth and chemoresistance.
  • Cell apoptosis, cell cycle progression, Bcl-xl expression, and nuclear factor-κB (NF-κB) activity were analyzed.

Main Results:

  • Fn14 was expressed in 50.98% of SCLC cases and associated with advanced pathologic stage and shorter survival.
  • Overexpression of Fn14 promoted SCLC cell growth, enhanced multidrug resistance, decreased apoptosis, and increased G2-phase accumulation.
  • Inhibition of Fn14 reduced cell growth, sensitized cells to chemotherapy, increased apoptosis, and induced G1/S phase arrest, mediated by the NF-κB/Bcl-xl pathway.

Conclusions:

  • Fn14 plays a significant role in promoting SCLC cell proliferation and chemoresistance.
  • The Fn14 signaling pathway, involving NF-κB and Bcl-xl, is a key mechanism in SCLC progression.
  • Fn14 represents a promising novel therapeutic target for SCLC treatment.

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