Tumor Biology

, Volume 35, Issue 9, pp 8633–8638 | Cite as

RETRACTED ARTICLE: FBXL5 targets cortactin for ubiquitination-mediated destruction to regulate gastric cancer cell migration

Research Article

Abstract

Cortactin, an actin-interacting protein, is implicated in cytoskeletal architecture and often amplified in several types of cancer including gastric adenocarcinomas. Downregulation of cortactin decreases cell migration and invasion. However, how to regulate cortactin in gastric cancer remains largely unknown. Here, we report that FBXL5 interacts with and targets cortactin for ubiquitylation and subsequent proteasomal degradation. Furthermore, we showed that FBXL5-induced cortactin degradation is mediated by extracellular regulated signal kinase (ERK). Serine phosphorylation sites mutant, cortactinS405A/S418A, prevent FBXL5-induced cortactin degradation. Moreover, CortactinS405A/S418A exhibited stronger effects in promoting gastric cancer cell migration when compared to wild-type cortactin. Taken together, our data suggested a novel molecular mechanism for the negative regulation of cortactin by FBXL5 in gastric cancer cells migration.

Keywords

FBXL5 Cortactin Ubiquitylation Gastric cancer 

Notes

Conflict of interest

None

References

  1. 1.
    Villanueva MT. Combination therapy: Update on gastric cancer in East Asia. Nat Rev Clin Oncol. 2011;8:690.CrossRefPubMedGoogle Scholar
  2. 2.
    Smyth EC, Cunningham D. Gastric cancer in 2012: Defining treatment standards and novel insights into disease biology. Nat Rev Clin Oncol. 2013;10:73–4.CrossRefPubMedGoogle Scholar
  3. 3.
    Yakirevich E, Resnick MB. Pathology of gastric cancer and its precursor lesions. Gastroenterol Clin N Am. 2013;42:261–84.CrossRefGoogle Scholar
  4. 4.
    Wu H, Parsons JT. Cortactin, an 80/85-kilodalton pp60src substrate, is a filamentous actin-binding protein enriched in the cell cortex. J Cell Biol. 1993;120:1417–26.CrossRefPubMedGoogle Scholar
  5. 5.
    MacGrath SM, Koleske AJ. Cortactin in cell migration and cancer at a glance. J Cell Sci. 2012;125:1621–6.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Huang C, Liu J, Haudenschild CC, Zhan X. The role of tyrosine phosphorylation of cortactin in the locomotion of endothelial cells. J Biol Chem. 1998;273:25770–6.CrossRefPubMedGoogle Scholar
  7. 7.
    Zhao J, Wei J, Mialki R, Zou C, Mallampalli RK, Zhao Y. Extracellular signal-regulated kinase (erk) regulates cortactin ubiquitination and degradation in lung epithelial cells. J Biol Chem. 2012;287:19105–14.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Liu B, Zheng Y, Wang TD, Xu HZ, Xia L, Zhang J, et al. Proteomic identification of common scf ubiquitin ligase fbxo6-interacting glycoproteins in three kinds of cells. J Proteome Res. 2012;11:1773–81.CrossRefPubMedGoogle Scholar
  9. 9.
    Skaar JR, Pagan JK, Pagano M. Mechanisms and function of substrate recruitment by f-box proteins. Nat Rev Mol Cell Biol. 2013;14:369–81.CrossRefPubMedGoogle Scholar
  10. 10.
    Hsiang CY, Wu SL, Ho TY. Activation of activator protein 1 and extracellular signal-regulated kinases in human hepatocellular transformation. Tumour Biol J Int Soc Oncodev Biol Medic. 2004;25:313–20.CrossRefGoogle Scholar
  11. 11.
    Folio C, Zalacain M, Zandueta C, Ormazabal C, Sierrasesumaga L, San Julian M, et al. cortactin (cttn) overexpression in osteosarcoma correlates with advanced stage and reduced survival. Cancer Biomark Sect A Dis Markers. 2011;10:35–41.CrossRefGoogle Scholar
  12. 12.
    Ambrosio EP, Rosa FE, Domingues MA, Villacis RA, Coudry Rde A, Tagliarini JV, et al. cortactin is associated with perineural invasion in the deep invasive front area of laryngeal carcinomas. Hum Pathol. 2011;42:1221–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Ruiz JC, Walker SD, Anderson SA, Eisenstein RS, Bruick RK. F-box and leucine-rich repeat protein 5 (fbxl5) is required for maintenance of cellular and systemic iron homeostasis. J Biol Chem. 2013;288:552–60.CrossRefPubMedGoogle Scholar
  14. 14.
    Moroishi T, Nishiyama M, Takeda Y, Iwai K, Nakayama KI. The fbxl5-irp2 axis is integral to control of iron metabolism in vivo. Cell Metab. 2011;14:339–51.CrossRefPubMedGoogle Scholar
  15. 15.
    Vashisht AA, Zumbrennen KB, Huang X, Powers DN, Durazo A, Sun D, et al. Control of iron homeostasis by an iron-regulated ubiquitin ligase. Science. 2009;326:718–21.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Salahudeen AA, Thompson JW, Ruiz JC, Ma HW, Kinch LN, Li Q, et al. An e3 ligase possessing an iron-responsive hemerythrin domain is a regulator of iron homeostasis. Science. 2009;326:722–6.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Roskoski Jr R. Erk1/2 map kinases: Structure, function, and regulation. Pharmacolo Res Off J Ital Pharmacol Soc. 2012;66:105–43.Google Scholar
  18. 18.
    Kim SK, Abdelmegeed MA, Novak RF. The mitogen-activated protein kinase kinase (mek) inhibitor pd98059 elevates primary cultured rat hepatocyte glutathione levels independent of inhibiting mek. Drug Metab Dispos Biol Fate Chem. 2006;34:683–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Mezi S, Todi L, Orsi E, Angeloni A, Mancini P. Involvement of the src-cortactin pathway in migration induced by igf-1 and egf in human breast cancer cells. Int J Oncol. 2012;41:2128–38.PubMedGoogle Scholar
  20. 20.
    Nakane K, Fujita Y, Terazawa R, Atsumi Y, Kato T, Nozawa Y, et al. Inhibition of cortactin and sirt1 expression attenuates migration and invasion of prostate cancer du145 cells. Int J Urol Off J Jpn Urol Assoc. 2012;19:71–9.Google Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of General SurgeryThe First People’s Hospital Affiliated to Shanghai JiaoTong UniversityShanghaiChina
  2. 2.Department of oncologyThe First People’s Hospital Affiliated to Shanghai JiaoTong UniversityShanghaiChina
  3. 3.Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina

Personalised recommendations