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A Rising Cancer Prevention Target of RSK2 in Human Skin Cancer

Narayanasamy Arul1, Yong-Yeon Cho

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

Frontiers in Oncology
|August 13, 2013
PubMed

Insights

Ribosomal S6 kinase 2 (RSK2) drives skin cancer by promoting cell proliferation and transformation. Natural compounds like kaempferol and eriodictyol show potential for targeting RSK2 in skin cancer prevention and treatment.

Area of Science:

  • Molecular Biology
  • Oncology
  • Dermatology

Background:

  • p90 ribosomal S6 kinase 2 (RSK2) is a serine/threonine kinase involved in cell proliferation and transformation.
  • RSK2 activation is triggered by growth factors like EGF and environmental stresses such as UV radiation.
  • RSK2 signaling pathways are implicated in various cellular processes, including cell cycle progression.

Purpose of the Study:

  • To investigate the role of RSK2 in human skin cancer development.
  • To explore the potential of natural compounds as RSK2 inhibitors for chemoprevention and therapy.

Main Methods:

  • Investigated RSK2 activation by EGF and UV via extracellular-activated protein kinases (eAPK) signaling.
  • Utilized siRNA and shRNA to knockdown RSK2 expression in human skin keratinocytes and melanoma cells.
  • Quantified RSK2 protein levels in human skin cancer tissues.
  • Assessed the inhibitory effects of kaempferol and eriodictyol on RSK2 kinase activity.

Main Results:

  • RSK2 activation by EGF and UV promotes cell cycle progression, proliferation, and anchorage-independent transformation.
  • RSK2 knockdown abrogates proliferation and transformation in non-malignant keratinocytes and inhibits melanoma cell growth.
  • Elevated RSK2 protein levels were observed in squamous cell carcinoma, basal-cell carcinoma, and melanoma tissues.
  • Kaempferol and eriodictyol inhibit the kinase activity of the RSK2 N-terminal domain.

Conclusions:

  • RSK2 plays a critical role in human skin cancer pathogenesis.
  • Targeting RSK2 with natural inhibitors like kaempferol and eriodictyol presents a promising strategy for skin cancer chemoprevention and therapy.
Keywords:
RSK2RSK2 inhibitorscarcinogenesischemopreventionskin cancer

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