Intracellular targeting of annexin A2 inhibits tumor cell adhesion, migration, and in vivo grafting
Abstract Cytoskeletal-associated proteins play an active role in coordinating the adhesion and migration machinery in cancer progression. To identify functional protein networks and potential inhibitors, we screened an internalizing phage (iPhage) display library in tumor cells, and selected LGRFYAA...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2017
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/5856840a50164afb9f65b36ea3d9f06a |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:5856840a50164afb9f65b36ea3d9f06a |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:5856840a50164afb9f65b36ea3d9f06a2021-12-02T12:32:50ZIntracellular targeting of annexin A2 inhibits tumor cell adhesion, migration, and in vivo grafting10.1038/s41598-017-03470-w2045-2322https://doaj.org/article/5856840a50164afb9f65b36ea3d9f06a2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03470-whttps://doaj.org/toc/2045-2322Abstract Cytoskeletal-associated proteins play an active role in coordinating the adhesion and migration machinery in cancer progression. To identify functional protein networks and potential inhibitors, we screened an internalizing phage (iPhage) display library in tumor cells, and selected LGRFYAASG as a cytosol-targeting peptide. By affinity purification and mass spectrometry, intracellular annexin A2 was identified as the corresponding binding protein. Consistently, annexin A2 and a cell-internalizing, penetratin-fused version of the selected peptide (LGRFYAASG-pen) co-localized and specifically accumulated in the cytoplasm at the cell edges and cell-cell contacts. Functionally, tumor cells incubated with LGRFYAASG-pen showed disruption of filamentous actin, focal adhesions and caveolae-mediated membrane trafficking, resulting in impaired cell adhesion and migration in vitro. These effects were paralleled by a decrease in the phosphorylation of both focal adhesion kinase (Fak) and protein kinase B (Akt). Likewise, tumor cells pretreated with LGRFYAASG-pen exhibited an impaired capacity to colonize the lungs in vivo in several mouse models. Together, our findings demonstrate an unrecognized functional link between intracellular annexin A2 and tumor cell adhesion, migration and in vivo grafting. Moreover, this work uncovers a new peptide motif that binds to and inhibits intracellular annexin A2 as a candidate therapeutic lead for potential translation into clinical applications.Daniela I. StaquiciniRoberto RangelLiliana Guzman-RojasFernanda I. StaquiciniAndrey S. DobroffChristy A. TarletonMichelle A. OzbunMikhail G. KoloninJuri G. GelovaniSerena MarchiòRichard L. SidmanKatherine A. HajjarWadih ArapRenata PasqualiniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Daniela I. Staquicini Roberto Rangel Liliana Guzman-Rojas Fernanda I. Staquicini Andrey S. Dobroff Christy A. Tarleton Michelle A. Ozbun Mikhail G. Kolonin Juri G. Gelovani Serena Marchiò Richard L. Sidman Katherine A. Hajjar Wadih Arap Renata Pasqualini Intracellular targeting of annexin A2 inhibits tumor cell adhesion, migration, and in vivo grafting |
| description |
Abstract Cytoskeletal-associated proteins play an active role in coordinating the adhesion and migration machinery in cancer progression. To identify functional protein networks and potential inhibitors, we screened an internalizing phage (iPhage) display library in tumor cells, and selected LGRFYAASG as a cytosol-targeting peptide. By affinity purification and mass spectrometry, intracellular annexin A2 was identified as the corresponding binding protein. Consistently, annexin A2 and a cell-internalizing, penetratin-fused version of the selected peptide (LGRFYAASG-pen) co-localized and specifically accumulated in the cytoplasm at the cell edges and cell-cell contacts. Functionally, tumor cells incubated with LGRFYAASG-pen showed disruption of filamentous actin, focal adhesions and caveolae-mediated membrane trafficking, resulting in impaired cell adhesion and migration in vitro. These effects were paralleled by a decrease in the phosphorylation of both focal adhesion kinase (Fak) and protein kinase B (Akt). Likewise, tumor cells pretreated with LGRFYAASG-pen exhibited an impaired capacity to colonize the lungs in vivo in several mouse models. Together, our findings demonstrate an unrecognized functional link between intracellular annexin A2 and tumor cell adhesion, migration and in vivo grafting. Moreover, this work uncovers a new peptide motif that binds to and inhibits intracellular annexin A2 as a candidate therapeutic lead for potential translation into clinical applications. |
| format |
article |
| author |
Daniela I. Staquicini Roberto Rangel Liliana Guzman-Rojas Fernanda I. Staquicini Andrey S. Dobroff Christy A. Tarleton Michelle A. Ozbun Mikhail G. Kolonin Juri G. Gelovani Serena Marchiò Richard L. Sidman Katherine A. Hajjar Wadih Arap Renata Pasqualini |
| author_facet |
Daniela I. Staquicini Roberto Rangel Liliana Guzman-Rojas Fernanda I. Staquicini Andrey S. Dobroff Christy A. Tarleton Michelle A. Ozbun Mikhail G. Kolonin Juri G. Gelovani Serena Marchiò Richard L. Sidman Katherine A. Hajjar Wadih Arap Renata Pasqualini |
| author_sort |
Daniela I. Staquicini |
| title |
Intracellular targeting of annexin A2 inhibits tumor cell adhesion, migration, and in vivo grafting |
| title_short |
Intracellular targeting of annexin A2 inhibits tumor cell adhesion, migration, and in vivo grafting |
| title_full |
Intracellular targeting of annexin A2 inhibits tumor cell adhesion, migration, and in vivo grafting |
| title_fullStr |
Intracellular targeting of annexin A2 inhibits tumor cell adhesion, migration, and in vivo grafting |
| title_full_unstemmed |
Intracellular targeting of annexin A2 inhibits tumor cell adhesion, migration, and in vivo grafting |
| title_sort |
intracellular targeting of annexin a2 inhibits tumor cell adhesion, migration, and in vivo grafting |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/5856840a50164afb9f65b36ea3d9f06a |
| work_keys_str_mv |
AT danielaistaquicini intracellulartargetingofannexina2inhibitstumorcelladhesionmigrationandinvivografting AT robertorangel intracellulartargetingofannexina2inhibitstumorcelladhesionmigrationandinvivografting AT lilianaguzmanrojas intracellulartargetingofannexina2inhibitstumorcelladhesionmigrationandinvivografting AT fernandaistaquicini intracellulartargetingofannexina2inhibitstumorcelladhesionmigrationandinvivografting AT andreysdobroff intracellulartargetingofannexina2inhibitstumorcelladhesionmigrationandinvivografting AT christyatarleton intracellulartargetingofannexina2inhibitstumorcelladhesionmigrationandinvivografting AT michelleaozbun intracellulartargetingofannexina2inhibitstumorcelladhesionmigrationandinvivografting AT mikhailgkolonin intracellulartargetingofannexina2inhibitstumorcelladhesionmigrationandinvivografting AT juriggelovani intracellulartargetingofannexina2inhibitstumorcelladhesionmigrationandinvivografting AT serenamarchio intracellulartargetingofannexina2inhibitstumorcelladhesionmigrationandinvivografting AT richardlsidman intracellulartargetingofannexina2inhibitstumorcelladhesionmigrationandinvivografting AT katherineahajjar intracellulartargetingofannexina2inhibitstumorcelladhesionmigrationandinvivografting AT wadiharap intracellulartargetingofannexina2inhibitstumorcelladhesionmigrationandinvivografting AT renatapasqualini intracellulartargetingofannexina2inhibitstumorcelladhesionmigrationandinvivografting |
| _version_ |
1718393919894454272 |