Brick1 is an essential regulator of actin cytoskeleton required for embryonic development and cell transformation

Beatriz Escobar, Guillermo De Cárcer, Gonzalo Fernández-Miranda, Alberto Cascón, José J. Bravo-Cordero, María C. Montoya, Mercedes Robledo, Marta Cañamero, Marcos Malumbres

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Brick1 (Brk1) is the less-studied component of the Wave/Scar pathway involved in the branched nucleation of actin fibers. The clinical relevance of Brk1 is emphasized by correlative data showing that Von Hippel-Lindau (VHL) patients that also lose the BRK1 gene are protected against the development of tumors. This contrasts with recent evidence suggesting that the Wave complex may function as an invasion suppressor in epithelial cancers. Here, we show that the downregulation of Brk1 results in abnormal actin stress fiber formation and vinculin distribution and loss of Arp2/3 and Wave proteins at the cellular protrusions. Brk1 is required for cell proliferation and cell transformation by oncogenes. In addition, Brk1 downregulation results in defective directional migration and invasive growth in renal cell carcinoma cells as well as in other tumor cell types. Finally, genetic ablation of Brk1 results in dramatic defects in embryo compaction and development, suggesting an essential role for this protein in actin dynamics. Thus, genetic loss or inhibition of BRK1 is likely to be protective against tumor development due to proliferation and motility defects in affected cells.

Original languageEnglish (US)
Pages (from-to)9349-9359
Number of pages11
JournalCancer Research
Volume70
Issue number22
DOIs
StatePublished - Nov 15 2010
Externally publishedYes

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Actin Cytoskeleton
Embryonic Development
Actins
Neoplasms
Cell Surface Extensions
Down-Regulation
Vinculin
Stress Fibers
Oncogenes
Renal Cell Carcinoma
Cicatrix
Proteins
Cell Proliferation
Growth
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Escobar, B., De Cárcer, G., Fernández-Miranda, G., Cascón, A., Bravo-Cordero, J. J., Montoya, M. C., ... Malumbres, M. (2010). Brick1 is an essential regulator of actin cytoskeleton required for embryonic development and cell transformation. Cancer Research, 70(22), 9349-9359. https://doi.org/10.1158/0008-5472.CAN-09-4491

Brick1 is an essential regulator of actin cytoskeleton required for embryonic development and cell transformation. / Escobar, Beatriz; De Cárcer, Guillermo; Fernández-Miranda, Gonzalo; Cascón, Alberto; Bravo-Cordero, José J.; Montoya, María C.; Robledo, Mercedes; Cañamero, Marta; Malumbres, Marcos.

In: Cancer Research, Vol. 70, No. 22, 15.11.2010, p. 9349-9359.

Research output: Contribution to journalArticle

Escobar, B, De Cárcer, G, Fernández-Miranda, G, Cascón, A, Bravo-Cordero, JJ, Montoya, MC, Robledo, M, Cañamero, M & Malumbres, M 2010, 'Brick1 is an essential regulator of actin cytoskeleton required for embryonic development and cell transformation', Cancer Research, vol. 70, no. 22, pp. 9349-9359. https://doi.org/10.1158/0008-5472.CAN-09-4491
Escobar B, De Cárcer G, Fernández-Miranda G, Cascón A, Bravo-Cordero JJ, Montoya MC et al. Brick1 is an essential regulator of actin cytoskeleton required for embryonic development and cell transformation. Cancer Research. 2010 Nov 15;70(22):9349-9359. https://doi.org/10.1158/0008-5472.CAN-09-4491
Escobar, Beatriz ; De Cárcer, Guillermo ; Fernández-Miranda, Gonzalo ; Cascón, Alberto ; Bravo-Cordero, José J. ; Montoya, María C. ; Robledo, Mercedes ; Cañamero, Marta ; Malumbres, Marcos. / Brick1 is an essential regulator of actin cytoskeleton required for embryonic development and cell transformation. In: Cancer Research. 2010 ; Vol. 70, No. 22. pp. 9349-9359.
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