Role and Characterization of Synuclein-γ Unconventional Protein Secretion in Cancer Cells

  • Caiyun Liu
  • Like Qu
  • Chengchao Shou
Part of the Methods in Molecular Biology book series (MIMB, volume 1459)


Synuclein-γ (SNCG), the third member of synuclein family, is implicated in both neurodegenerative diseases and cancer. Overexpression of SNCG in cancer cells is linked to tumor progression and chemoresistance. Without any known signal sequence required for conventional protein secretion, SNCG is elevated in the serum of cancer patients and the medium of cultured cancer cells. SNCG actively secretes from cancer cells and extracellular SNCG promotes malignant phenotypes of cancer cells. Here, we describe methods for the characterization of SNCG as an unconventional secretion protein from cancer cells and investigation of the effect of extracellular SNCG on the phenotypes of cancer cells.

Key words

Synuclein-γ Unconventional secretion Cancer cell Migration Invasion 



This work was supported by the National Natural Science Foundation of China (No. 81272410).


  1. 1.
    Shi YE, Chen Y, Dackour R et al (2010) Synuclein gamma stimulates membrane-initiated estrogen signaling by chaperoning estrogen receptor (ER)-alpha36, a variant of ER-alpha. Am J Pathol 177:964–973CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Liang W, Miao S, Zhang B et al (2015) Synuclein γ protects Akt and mTOR and renders tumor resistance to Hsp90 disruption. Oncogene 34:2398–2405CrossRefPubMedGoogle Scholar
  3. 3.
    Li M, Yin Y, Hua H et al (2010) The reciprocal regulation of gamma-synuclein and IGF-I receptor expression creates a circuit that modulates IGF-I signaling. J Biol Chem 285:30480–30488CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Pan ZZ, Bruening W, Giasson BI et al (2002) Gamma-synuclein promotes cancer cell survival and inhibits stress- and chemotherapy drug-induced apoptosis by modulating MAPK pathways. J Biol Chem 277:35050–35060CrossRefPubMedGoogle Scholar
  5. 5.
    Zhang H, Kouadio A, Cartledge D et al (2011) Role of gamma-synuclein in microtubule regulation. Exp Cell Res 317:1330–1339CrossRefPubMedGoogle Scholar
  6. 6.
    Li Z, Sclabas GM, Peng B et al (2004) Overexpression of synuclein-gamma in pancreatic adenocarcinoma. Cancer 101:58–65CrossRefPubMedGoogle Scholar
  7. 7.
    Liu C, Guo J, Qu L et al (2008) Applications of novel monoclonal antibodies specific for synuclein-gamma in evaluating its levels in sera and cancer tissues from colorectal cancer patients. Cancer Lett 269:148–158CrossRefPubMedGoogle Scholar
  8. 8.
    Liu C, Ma H, Qu L et al (2012) Elevated serum synuclein-gamma in patients with gastrointestinal and esophageal carcinomas. Hepatogastroenterology 59:2222–2227PubMedGoogle Scholar
  9. 9.
    Liu C, Qu L, Lian S et al (2014) Unconventional secretion of synuclein-γ promotes tumor cell invasion. FEBS J 281:5159–5171CrossRefPubMedGoogle Scholar
  10. 10.
    Nickel W, Rabouille C (2009) Mechanisms of regulated unconventional protein secretion. Nat Rev Mol Cell Biol 10:148–155CrossRefPubMedGoogle Scholar
  11. 11.
    Villarreal L, Méndez O, Salvans C et al (2013) Unconventional secretion is a major contributor of cancer cell line secretomes. Mol Cell Proteomics 12:1046–1060CrossRefPubMedGoogle Scholar
  12. 12.
    Zhang M, Schekman R (2013) Cell biology. Unconventional secretion, unconventional solutions. Science 340:559–561CrossRefPubMedGoogle Scholar
  13. 13.
    Merendino AM, Bucchieri F, Campanella C et al (2010) Hsp60 is actively secreted by human tumor cells. PLoS One 5, e9247CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Savina A, Furla′n M, Vidal M et al (2003) Exosome release is regulated by a calcium-dependent mechanism in K562 cells. J Biol Chem 278:20083–20090CrossRefPubMedGoogle Scholar
  15. 15.
    Lancaster GI, Febbraio MA (2005) Exosome-dependent trafficking of HSP-70: a novel secretory pathway for cellular stress proteins. J Biol Chem 280:23349–23355CrossRefPubMedGoogle Scholar
  16. 16.
    Danielsen EM, van Deurs B, Hansen GH (2003) “Nonclassical” secretion of annexin A2 to the lumenal side of the enterocyte brush border membrane. Biochemistry 42:14670–14676CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education)Peking University Cancer Hospital & InstituteBeijingChina
  2. 2.Department of Biochemistry & Molecular BiologyPeking University Cancer Hospital & InstituteBeijingChina

Personalised recommendations