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Palmitoylated SCP1 is targeted to the plasma membrane and negatively regulates angiogenesis

Peng Liao1,2, Weichao Wang1,2, Yu Li2

  • 1Department of Central Laboratory, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Elife
|April 26, 2017
PubMed

Insights

SCP1 protein regulates genes in the nucleus but also suppresses cancer by dephosphorylating AKT at the plasma membrane, reducing angiogenesis and tumor growth.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • SCP1 (SCP1) is known as a nuclear transcriptional regulator.
  • Its role in cancer and plasma membrane localization is largely unexplored.

Purpose of the Study:

  • To investigate the novel function of SCP1 as a plasma membrane protein in cancer cells.
  • To elucidate the mechanism by which membrane-localized SCP1 affects AKT signaling, angiogenesis, and tumorigenesis.

Main Methods:

  • Utilized EGFP- or epitope-fused SCP1 to visualize its localization in cancer cells.
  • Examined AKT phosphorylation at serine 473 and its impact on angiogenesis and tumor growth.
  • Investigated the role of SCP1 palmitoylation for its membrane localization using knockout mice.

Main Results:

  • SCP1 was found to localize to the plasma membrane in various cancer cells.
  • Membrane-localized SCP1 dephosphorylates AKT at serine 473, suppressing angiogenesis and tumorigenesis.
  • SCP1 gene knockout mice exhibited increased AKT phosphorylation, angiogenesis, and tumor growth.
  • Palmitoylation of a conserved cysteine motif in SCP1's N-terminus is critical for its membrane localization.

Conclusions:

  • SCP1 exhibits a dual role, acting as both a nuclear regulator and a plasma membrane protein.
  • Membrane-localized SCP1 dephosphorylates AKT, providing a novel mechanism to suppress angiogenesis and tumor growth.
  • SCP1's shuttling between the nucleus and plasma membrane offers a unique pathway for transducing AKT signaling relevant to cancer development.
Keywords:
angiogenesiscancer biologycell biologyhuman cancer cell linesmousetumorigenesis

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