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Inhibitory cortactin nanobodies delineate the role of NTA- and SH3-domain-specific functions during invadopodium formation and cancer cell invasion

Laurence Bertier (UGent) , Ciska Boucherie (UGent) , Olivier Zwaenepoel (UGent) , Berlinda Vanloo (UGent) , Marleen Van Troys (UGent) , Isabel Van Audenhove (UGent) and Jan Gettemans (UGent)
(2017) FASEB JOURNAL. 31(6). p.2460-2476
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Abstract
Cancer cells exploit different strategies to escape from the primary tumor, gain access to the circulation, disseminate throughout the body, and form metastases, the leading cause of death by cancer. Invadopodia, proteolytically active plasma membrane extensions, are essential in this escape mechanism. Cortactin is involved in every phase of invadopodia formation, and its overexpression is associated with increased invadopodia formation, extracellular matrix degradation, and cancer cell invasion. To analyze endogenous cortactin domain function in these processes, we characterized the effects of nanobodies that are specific for the N-terminal acidic domain of cortactin and expected to target small epitopes within this domain. These nanobodies inhibit cortactin-mediated actin-related protein (Arp) 2/3 activation, and, after their intracellular expression in cancer cells, decrease invadopodia formation, extracellular matrix degradation, and cancer cell invasion. In addition, one of the nanobodies affects Arp2/3 interaction and invadopodium stability, and a nanobody targeting the Src homology 3 domain of cortactin enabled comparison of 2 functional regions in invadopodium formation or stability. Given their common and distinct effects, we validate cortactin nanobodies as an instrument to selectively block and study distinct domains within a protein with unprecedented precision, aiding rational future generation of protein domain-selective therapeutic compounds.
Keywords
single domain antibody, intrabody, actin, Arp2/3 complex, matrix metalloprotease: EXTRACELLULAR-MATRIX DEGRADATION, SMALL-MOLECULE INHIBITORS, ARP2/3 COMPLEX, N-WASP, INTRACELLULAR ANTIBODIES, PERICELLULAR PROTEOLYSIS, ACTIN POLYMERIZATION, FAMILY PROTEINS, F-ACTIN, MATURATION

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Chicago
Bertier, Laurence, Ciska Boucherie, Olivier Zwaenepoel, Berlinda Vanloo, Marleen Van Troys, Isabel Van Audenhove, and Jan Gettemans. 2017. “Inhibitory Cortactin Nanobodies Delineate the Role of NTA- and SH3-domain-specific Functions During Invadopodium Formation and Cancer Cell Invasion.” Faseb Journal 31 (6): 2460–2476.
APA
Bertier, Laurence, Boucherie, C., Zwaenepoel, O., Vanloo, B., Van Troys, M., Van Audenhove, I., & Gettemans, J. (2017). Inhibitory cortactin nanobodies delineate the role of NTA- and SH3-domain-specific functions during invadopodium formation and cancer cell invasion. FASEB JOURNAL, 31(6), 2460–2476.
Vancouver
1.
Bertier L, Boucherie C, Zwaenepoel O, Vanloo B, Van Troys M, Van Audenhove I, et al. Inhibitory cortactin nanobodies delineate the role of NTA- and SH3-domain-specific functions during invadopodium formation and cancer cell invasion. FASEB JOURNAL. 2017;31(6):2460–76.
MLA
Bertier, Laurence, Ciska Boucherie, Olivier Zwaenepoel, et al. “Inhibitory Cortactin Nanobodies Delineate the Role of NTA- and SH3-domain-specific Functions During Invadopodium Formation and Cancer Cell Invasion.” FASEB JOURNAL 31.6 (2017): 2460–2476. Print.
@article{8511280,
  abstract     = {Cancer cells exploit different strategies to escape from the primary tumor, gain access to the circulation, disseminate throughout the body, and form metastases, the leading cause of death by cancer. Invadopodia, proteolytically active plasma membrane extensions, are essential in this escape mechanism. Cortactin is involved in every phase of invadopodia formation, and its overexpression is associated with increased invadopodia formation, extracellular matrix degradation, and cancer cell invasion. To analyze endogenous cortactin domain function in these processes, we characterized the effects of nanobodies that are specific for the N-terminal acidic domain of cortactin and expected to target small epitopes within this domain. These nanobodies inhibit cortactin-mediated actin-related protein (Arp) 2/3 activation, and, after their intracellular expression in cancer cells, decrease invadopodia formation, extracellular matrix degradation, and cancer cell invasion. In addition, one of the nanobodies affects Arp2/3 interaction and invadopodium stability, and a nanobody targeting the Src homology 3 domain of cortactin enabled comparison of 2 functional regions in invadopodium formation or stability. Given their common and distinct effects, we validate cortactin nanobodies as an instrument to selectively block and study distinct domains within a protein with unprecedented precision, aiding rational future generation of protein domain-selective therapeutic compounds.},
  author       = {Bertier, Laurence and Boucherie, Ciska and Zwaenepoel, Olivier and Vanloo, Berlinda and Van Troys, Marleen and Van Audenhove, Isabel and Gettemans, Jan},
  issn         = {0892-6638},
  journal      = {FASEB JOURNAL},
  language     = {eng},
  number       = {6},
  pages        = {2460--2476},
  title        = {Inhibitory cortactin nanobodies delineate the role of NTA- and SH3-domain-specific functions during invadopodium formation and cancer cell invasion},
  url          = {http://dx.doi.org/10.1096/fj.201600810rr},
  volume       = {31},
  year         = {2017},
}

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