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FOSB⁻PCDHB13 Axis Disrupts the Microtubule Network in Non-Small Cell Lung Cancer

Chen-Hung Ting1, Kang-Yun Lee2,3,4, Sheng-Ming Wu5,6

  • 1Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, Ilan 262, Taiwan. koichiting@gmail.com.

Cancers
|January 20, 2019
PubMed

Insights

FBJ murine osteosarcoma viral oncogene homolog B (FOSB) and protocadherin-β13 (PCDHB13) act as tumor suppressors in non-small cell lung cancer (NSCLC). Their downregulation in NSCLC patients suggests a novel therapeutic pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Non-small cell lung cancer (NSCLC) presents a significant global health challenge, with high mortality rates often exacerbated by drug resistance.
  • Developing novel therapeutic strategies requires a deeper understanding of NSCLC pathogenesis and the identification of new molecular targets.

Purpose of the Study:

  • To investigate the role of FBJ murine osteosarcoma viral oncogene homolog B (FOSB) and its downstream targets in non-small cell lung cancer (NSCLC).
  • To explore the potential of the FOSB-PCDHB13 axis as a novel tumor suppressive pathway in NSCLC.

Main Methods:

  • Induction of FOSB by tilapia piscidin-4 (TP4) and its effect on mitochondrial calcium homeostasis in NSCLC cells.
  • Transcriptomic analysis, ChIP-qPCR, and immunocytochemistry to identify FOSB targets, including protocadherin-β13 (PCDHB13).
  • In vitro and in vivo studies to assess the impact of FOSB and PCDHB13 overexpression on NSCLC growth and survival.

Main Results:

  • FBJ murine osteosarcoma viral oncogene homolog B (FOSB) was induced by tilapia piscidin-4 (TP4), impacting mitochondrial calcium (Ca2+) homeostasis in NSCLC cells.
  • Protocadherin-β13 (PCDHB13) was identified as a FOSB target functionally linked to microtubules.
  • Overexpression of FOSB or PCDHB13 inhibited NSCLC cell growth and survival both in vitro and in vivo.
  • Downregulation of FOSB and PCDHB13 was observed in NSCLC patient samples and correlated with higher pathological grade.

Conclusions:

  • The FOSB-PCDHB13 signaling axis represents a novel tumor suppressive pathway in non-small cell lung cancer.
  • FOSB induction by TP4 and its downstream effects on PCDHB13 offer potential therapeutic targets for NSCLC treatment.
  • The observed downregulation of FOSB and PCDHB13 in patients highlights their prognostic significance and therapeutic potential.
Keywords:
FOSBantimicrobial peptidecytoskeletonmitochondrial stressnon-small cell lung cancer (NSCLC)protocadherin

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