Advanced search
1 file | 3.21 MB Add to list

Nanobodies targeting cortactin proline rich, helical and actin binding regions downregulate invadopodium formation and matrix degradation in SCC-61 cancer cells

Author
Organization
Abstract
Cortactin is a multidomain actin binding protein that activates Arp2/3 mediated branched actin polymerization. This is essential for the formation of protrusive structures during cancer cell invasion. Invadopodia are cancer cell-specific membrane protrusions, specialized at extracellular matrix degradation and essential for invasion and tumor metastasis. Given the unequivocal role of cortactin at every stage of invadopodium formation, it is considered an invadopodium marker and potential drug target. We used cortactin nanobodies to examine the role of cortactin domain-specific function at endogenous protein level. Two cortactin nanobodies target the central region of cortactin with high specificity. One nanobody interacts with the actin binding repeats whereas the other targets the proline rich region and was found to reduce EGF-induced cortactin phosphorylation. After intracellular expression as an intrabody, they are both capable of tracing their target in the complex environment of the cytoplasm, and disturb cortactin functions during invadopodia formation and extracellular matrix degradation. These data illustrate the use of nanobodies as a research tool to dissect the role of cortactin in cancer cell motility. This information can contribute to the development of novel therapeutics for tumor cell migration and metastasis.
Keywords
Cortactin, Phosphorylation, Invadopodia, Metastasis, Nanobody, Intrabody, AMYLOIDOSIS MOUSE MODEL, ARP2/3 COMPLEX, TYROSINE PHOSPHORYLATION, EXOSOME SECRETION, FAMILY PROTEINS, HB-EGF, INVASION, METASTASIS, PROMOTES, MOTILITY

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • binary/octet-stream
    • |
    • 3.21 MB

Citation

Please use this url to cite or link to this publication:

MLA
Bertier, Laurence, Tim Hebbrecht, Elien Mettepenningen, et al. “Nanobodies Targeting Cortactin Proline Rich, Helical and Actin Binding Regions Downregulate Invadopodium Formation and Matrix Degradation in SCC-61 Cancer Cells.” BIOMEDICINE & PHARMACOTHERAPY 102 (2018): 230–241. Print.
APA
Bertier, Laurence, Hebbrecht, T., Mettepenningen, E., De Wit, N., Zwaenepoel, O., Verhelle, A., & Gettemans, J. (2018). Nanobodies targeting cortactin proline rich, helical and actin binding regions downregulate invadopodium formation and matrix degradation in SCC-61 cancer cells. BIOMEDICINE & PHARMACOTHERAPY, 102, 230–241.
Chicago author-date
Bertier, Laurence, Tim Hebbrecht, Elien Mettepenningen, Natasja De Wit, Olivier Zwaenepoel, Adriaan Verhelle, and Jan Gettemans. 2018. “Nanobodies Targeting Cortactin Proline Rich, Helical and Actin Binding Regions Downregulate Invadopodium Formation and Matrix Degradation in SCC-61 Cancer Cells.” Biomedicine & Pharmacotherapy 102: 230–241.
Chicago author-date (all authors)
Bertier, Laurence, Tim Hebbrecht, Elien Mettepenningen, Natasja De Wit, Olivier Zwaenepoel, Adriaan Verhelle, and Jan Gettemans. 2018. “Nanobodies Targeting Cortactin Proline Rich, Helical and Actin Binding Regions Downregulate Invadopodium Formation and Matrix Degradation in SCC-61 Cancer Cells.” Biomedicine & Pharmacotherapy 102: 230–241.
Vancouver
1.
Bertier L, Hebbrecht T, Mettepenningen E, De Wit N, Zwaenepoel O, Verhelle A, et al. Nanobodies targeting cortactin proline rich, helical and actin binding regions downregulate invadopodium formation and matrix degradation in SCC-61 cancer cells. BIOMEDICINE & PHARMACOTHERAPY. 2018;102:230–41.
IEEE
[1]
L. Bertier et al., “Nanobodies targeting cortactin proline rich, helical and actin binding regions downregulate invadopodium formation and matrix degradation in SCC-61 cancer cells,” BIOMEDICINE & PHARMACOTHERAPY, vol. 102, pp. 230–241, 2018.
@article{8566350,
  abstract     = {Cortactin is a multidomain actin binding protein that activates Arp2/3 mediated branched actin polymerization. This is essential for the formation of protrusive structures during cancer cell invasion. Invadopodia are cancer cell-specific membrane protrusions, specialized at extracellular matrix degradation and essential for invasion and tumor metastasis. Given the unequivocal role of cortactin at every stage of invadopodium formation, it is considered an invadopodium marker and potential drug target. We used cortactin nanobodies to examine the role of cortactin domain-specific function at endogenous protein level. Two cortactin nanobodies target the central region of cortactin with high specificity. One nanobody interacts with the actin binding repeats whereas the other targets the proline rich region and was found to reduce EGF-induced cortactin phosphorylation. After intracellular expression as an intrabody, they are both capable of tracing their target in the complex environment of the cytoplasm, and disturb cortactin functions during invadopodia formation and extracellular matrix degradation. These data illustrate the use of nanobodies as a research tool to dissect the role of cortactin in cancer cell motility. This information can contribute to the development of novel therapeutics for tumor cell migration and metastasis.},
  author       = {Bertier, Laurence and Hebbrecht, Tim and Mettepenningen, Elien and De Wit, Natasja and Zwaenepoel, Olivier and Verhelle, Adriaan and Gettemans, Jan},
  issn         = {0753-3322},
  journal      = {BIOMEDICINE & PHARMACOTHERAPY},
  keywords     = {Cortactin,Phosphorylation,Invadopodia,Metastasis,Nanobody,Intrabody,AMYLOIDOSIS MOUSE MODEL,ARP2/3 COMPLEX,TYROSINE PHOSPHORYLATION,EXOSOME SECRETION,FAMILY PROTEINS,HB-EGF,INVASION,METASTASIS,PROMOTES,MOTILITY},
  language     = {eng},
  pages        = {230--241},
  title        = {Nanobodies targeting cortactin proline rich, helical and actin binding regions downregulate invadopodium formation and matrix degradation in SCC-61 cancer cells},
  url          = {http://dx.doi.org/10.1016/j.biopha.2018.03.064},
  volume       = {102},
  year         = {2018},
}

Altmetric
View in Altmetric
Web of Science
Times cited: