CDCA7 finely tunes cytoskeleton dynamics to promote lymphoma migration and invasion

Metastases, the major cause of death from cancer, require cells' acquisition of the ability to migrate and involve multiple steps, including local tumor cell invasion and basement membrane penetration. Certain lymphoid tumors are highly metastatic, but the mechanisms of invasion by lymphoma cel...

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Bibliographic Details
Published in:Haematologica (Roma) 2020-03, Vol.105 (3), p.730-740
Main Authors: Martín-Cortázar, Carla, Chiodo, Yuri, Jiménez, Raul P, Bernabé, Manuel, Cayuela, María Luisa, Iglesias, Teresa, Campanero, Miguel R
Format: Article
Language:English
Subjects:
Animals
Carcinogenesis
Cell Line, Tumor
Cell Movement
Cytoskeleton
Lymphoma - genetics
Mice
Neoplasm Invasiveness
Zebrafish
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Summary:Metastases, the major cause of death from cancer, require cells' acquisition of the ability to migrate and involve multiple steps, including local tumor cell invasion and basement membrane penetration. Certain lymphoid tumors are highly metastatic, but the mechanisms of invasion by lymphoma cells are poorly understood. We recently showed that CDCA7, a protein induced by MYC, is overexpressed in lymphoid tumors and that its knockdown decreases lymphoid tumor growth without inhibiting the proliferation of normal cells. Here we show that CDCA7 is critical for invasion and migration of lymphoma cells. Indeed, CDCA7 knockdown in lymphoma cells limited tumor cell invasion in matrigel-coated transwell plates and tumor invasion of neighboring tissues in a mouse xenograft model and in a zebrafish model of cell invasion. CDCA7 silencing markedly inhibited lymphoma cell migration on fibronectin without modifying cell adhesion to this protein. Instead, CDCA7 knockdown markedly disrupted the precise dynamic reorganization of actomyosin and tubulin cytoskeletons required for efficient migration. In particular, CDCA7 silencing impaired tubulin and actomyosin cytoskeleton polarization, increased filamentous actin formation, and induced myosin activation. Of note, inhibitors of actin polymerization, myosin II, or ROCK reestablished the migration capacity of CDCA7-silenced lymphoma cells. Given the critical role of CDCA7 in lymphoma-genesis and invasion, therapies aimed at inhibiting its expression or activity might provide significant control of lymphoma growth, invasion, and metastatic dissemination.
ISSN:0390-6078
1592-8721
DOI:10.3324/haematol.2018.215459