Small GTPase Arl6 controls RH30 rhabdomyosarcoma cell growth through ciliogenesis and Hedgehog signaling

Xiaotong Liu1, Qiuhong Shen1, Tingting Yu1

  • 1Department of Developmental Genetics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166 Jiangsu People's Republic of China.

Cell & Bioscience
|December 22, 2016
PubMed
Abstract

Insights

ADP ribosylation factor like GTPase 6 (ARL6) is crucial for primary cilia formation and Hedgehog signaling in rhabdomyosarcoma. Targeting ARL6 may offer a new therapeutic strategy for this cancer.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Cancer Research

Background:

  • Rhabdomyosarcoma (RMS) arises from undifferentiated skeletal muscle precursors.
  • Hedgehog (Hh) signaling and primary cilia are implicated in RMS development.

Purpose of the Study:

  • To investigate the role of ADP ribosylation factor like GTPase 6 (ARL6) in ciliogenesis and Hh signaling within the context of RMS.

Main Methods:

  • Localization studies of ARL6 at primary cilia.
  • Analysis of Arl6 transcription during myoblast differentiation.
  • Assessment of ARL6 expression in RMS cells and tissues.
  • Investigating the effects of Arl6 knockdown on RMS cell proliferation, apoptosis, ciliogenesis, and Hh activity.

Main Results:

  • ARL6 localizes to the base of primary cilia and regulates ciliogenesis and Hh signaling.
  • Arl6 transcription changes dynamically with myoblast differentiation and primary cilia dynamics.
  • ARL6 expression is elevated in cilia-dependent RMS cells and tissues.
  • ARL6 knockdown in RH30 RMS cells reduced proliferation and increased apoptosis via impaired ciliogenesis and Hh signaling.

Conclusions:

  • ARL6 plays a significant role in ciliogenesis and Hh signaling.
  • The involvement of ARL6 in these processes suggests its potential as a therapeutic target for rhabdomyosarcoma.

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