Functional proteomics characterization of the role of SPRYD7 in colorectal cancer progression and metastasis

ABSTRACT: SPRY domain-containing protein 7 (SPRYD7) is a barely known protein identified by spatial proteomics as upregulated in highly-metastatic to liver KM12SM colorectal cancer (CRC) cells in comparison to its isogenic poorly-metastatic KM12C CRC cells. Here, we aimed at analyzing SPRYD7 role in CRC by functional proteomics. By immunohistochemistry, the overexpression of SPRYD7 was observed to be associated to poor survival of CRC patients, and to an aggressive and metastatic phenotype. SPRYD7 stably 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. After confirming the upregulation of SPRYD7, in vitro and in vivo functional assays confirmed a key role of SPRYD7 in proliferation and migration of CRC cells. Furthermore, SPRYD7 was observed as an inductor of angiogenesis. In addition, the dysregulated SPRYD7-associated proteome and SPRYD7 interactors were elucidated by 10-plex TMT quantitative proteins, immunoproteomics, and bioinformatics. After WB validation, the biological pathways associated to the stably overexpression of SPRYD7 were visualized. In conclusion, it was demonstrated here that SPRYD7 is a novel protein associated to CRC progression and metastasis. Thus, SPRYD7 and its interactors might be of relevance to identify novel therapeutic targets for advanced CRC.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Colon Cancer

SUBMITTER: Ana Montero Calle  

LAB HEAD: Rodrigo Barderas

PROVIDER: PXD042901 | Pride | 2024-01-26

REPOSITORIES: Pride