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Molecular Targeting of ERKs/RSK2 Signaling Axis in Cancer Prevention

Sun-Mi Yoo1, Sung Jun Cho2, Yong-Yeon Cho1

  • 1College of Pharmacy, The Catholic University of Korea, Bucheon, Korea.

Journal of Cancer Prevention
|October 17, 2015
PubMed

Insights

Ribosomal S6 Kinase 2 (RSK2) is crucial in cell proliferation and cancer development. Inhibiting the ERK/RSK2 pathway with compounds like kaempferol shows promise for cancer chemoprevention.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cancer Research

Background:

  • Ribosomal S6 Kinase 2 (RSK2) is a conserved signaling protein downstream of ERK1/ERK2, vital for physiological homeostasis.
  • RSK2 acts as a kinase upstream of transcription, epigenetic factors, cell cycle regulators, and protein synthesis.
  • RSK2 activation by growth factors drives cell proliferation, transformation, and cancer development.

Purpose of the Study:

  • To investigate the etiological role of RSK2 in human skin cancer development.
  • To explore the potential of targeting the ERK/RSK2 signaling axis for cancer chemoprevention.

Main Methods:

  • Analysis of RSK2 protein levels in skin cancer tissues versus normal tissues.
  • Investigating the effects of RSK2 ectopic expression and knockdown in JB6 Cl41 cells.
  • Evaluating the inhibitory effects of kaempferol on RSK2 activity and cell transformation.

Main Results:

  • Elevated total- and phospho-RSK2 levels, mediated by ERK1/ERK2, were observed in skin cancer tissues.
  • Ectopic RSK2 expression induced proliferation and anchorage-independent transformation; RSK2 knockdown suppressed these processes.
  • Kaempferol selectively inhibited RSK2 activity in epidermal growth factor-induced cell cycle transition and transformation.

Conclusions:

  • The ERK/RSK2 signaling pathway plays a significant role in skin cancer development.
  • Targeting RSK2, potentially with natural compounds like kaempferol, represents a viable strategy for cancer chemoprevention.
Keywords:
CarcinogenesisERKs/RSK2 signalingMolecular targetingNatural compoundsNeoplastic cell transformation

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