2026-06-14T03:44:49Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/167482024-11-28T19:03:04Zcom_20.500.12105_15322com_20.500.12105_2051com_20.500.12105_2052col_20.500.12105_16963col_20.500.12105_19617
Repisalud
author
Montero-Calle, Ana Maria
author
Jiménez de Ocaña, Sofía
author
Benavente-Naranjo, Ruth
author
Rejas-González, Raquel
author
Bartolomé, Rubén A
author
Martínez-Useros, Javier
author
Sanz, Rodrigo
author
Dziaková, Jana
author
Fernández-Aceñero, María Jesús
author
Mendiola, Marta
author
Casal, José Ignacio
author
Peláez-García, Alberto
author
Barderas Manchado, Rodrigo
funder
Agencia Estatal de Investigación (España)
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Ministerio de Educación, Cultura y Deporte (España)
2023-12-05T08:29:12Z
2023-12-05T08:29:12Z
2023-10-31
Cells. 2023 Oct 31;12(21):2548.
10.3390/cells12212548
2073-4409
Cells
37947626
http://hdl.handle.net/20.500.12105/16748
SPRY domain-containing protein 7 (SPRYD7) is a barely known protein identified via spatial proteomics as being upregulated in highly metastatic-to-liver KM12SM colorectal cancer (CRC) cells in comparison to its isogenic poorly metastatic KM12C CRC cells. Here, we aimed to analyze SPRYD7's role in CRC via functional proteomics. Through immunohistochemistry, the overexpression of SPRYD7 was observed to be associated with the poor survival of CRC patients and with an aggressive and metastatic phenotype. Stable SPRYD7 overexpression was performed in KM12C and SW480 poorly metastatic CRC cells and in their isogenic highly metastatic-to-liver-KM12SM-and-to-lymph-nodes SW620 CRC cells, respectively. Upon upregulation of SPRYD7, in vitro and in vivo functional assays confirmed a key role of SPRYD7 in the invasion and migration of CRC cells and in liver homing and tumor growth. Additionally, transient siRNA SPRYD7 silencing allowed us to confirm in vitro functional results. Furthermore, SPRYD7 was observed as an inductor of angiogenesis. In addition, the dysregulated SPRYD7-associated proteome and SPRYD7 interactors were elucidated via 10-plex TMT quantitative proteins, immunoproteomics, and bioinformatics. After WB validation, the biological pathways associated with the stable overexpression of SPRYD7 were visualized. In conclusion, it was demonstrated here that SPRYD7 is a novel protein associated with CRC progression and metastasis. Thus, SPRYD7 and its interactors might be of relevance in identifying novel therapeutic targets for advanced CRC.
eng
Colorectal cancer
SPRYD7
Cancermetastasis
Proteomics
Protein dysregulation
Interactome
Functional Proteomics Characterization of the Role of SPRYD7 in Colorectal Cancer Progression and Metastasis
research article
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