PMID- 37947626
OWN - NLM
STAT- MEDLINE
DCOM- 20231115
LR  - 20240201
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 12
IP  - 21
DP  - 2023 Oct 31
TI  - Functional Proteomics Characterization of the Role of SPRYD7 in Colorectal Cancer 
      Progression and Metastasis.
LID - 10.3390/cells12212548 [doi]
LID - 2548
AB  - 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.
FAU - Montero-Calle, Ana
AU  - Montero-Calle A
AUID- ORCID: 0000-0001-5141-0454
AD  - Chronic Disease Programme (UFIEC), Instituto de Salud Carlos III, 28220 Madrid, 
      Spain.
FAU - Jimenez de Ocana, Sofia
AU  - Jimenez de Ocana S
AD  - Chronic Disease Programme (UFIEC), Instituto de Salud Carlos III, 28220 Madrid, 
      Spain.
FAU - Benavente-Naranjo, Ruth
AU  - Benavente-Naranjo R
AD  - Chronic Disease Programme (UFIEC), Instituto de Salud Carlos III, 28220 Madrid, 
      Spain.
FAU - Rejas-Gonzalez, Raquel
AU  - Rejas-Gonzalez R
AUID- ORCID: 0000-0002-4614-2536
AD  - Chronic Disease Programme (UFIEC), Instituto de Salud Carlos III, 28220 Madrid, 
      Spain.
FAU - Bartolome, Ruben A
AU  - Bartolome RA
AUID- ORCID: 0000-0002-3292-1491
AD  - Centro de Investigaciones Biologicas Margarita Salas, CSIC, 28040 Madrid, Spain.
FAU - Martinez-Useros, Javier
AU  - Martinez-Useros J
AUID- ORCID: 0000-0001-9007-828X
AD  - Translational Oncology Division, OncoHealth Institute, Health Research 
      Institute-University Hospital Fundacion Jimenez Diaz-Universidad Autonoma de 
      Madrid, 28040 Madrid, Spain.
FAU - Sanz, Rodrigo
AU  - Sanz R
AD  - Surgical Digestive Department, Hospital Universitario Clinico San Carlos, 28040 
      Madrid, Spain.
FAU - Dziakova, Jana
AU  - Dziakova J
AUID- ORCID: 0000-0001-5317-5275
AD  - Surgical Digestive Department, Hospital Universitario Clinico San Carlos, 28040 
      Madrid, Spain.
FAU - Fernandez-Acenero, Maria Jesus
AU  - Fernandez-Acenero MJ
AUID- ORCID: 0000-0002-2439-3553
AD  - Surgical Pathology Department, Hospital Universitario Clinico San Carlos, 28040 
      Madrid, Spain.
FAU - Mendiola, Marta
AU  - Mendiola M
AD  - Molecular Pathology and Therapeutic Targets Group, La Paz University Hospital 
      (IdiPAZ), 28046 Madrid, Spain.
FAU - Casal, Jose Ignacio
AU  - Casal JI
AUID- ORCID: 0000-0003-1085-2840
AD  - Centro de Investigaciones Biologicas Margarita Salas, CSIC, 28040 Madrid, Spain.
FAU - Pelaez-Garcia, Alberto
AU  - Pelaez-Garcia A
AUID- ORCID: 0000-0002-5401-3216
AD  - Molecular Pathology and Therapeutic Targets Group, La Paz University Hospital 
      (IdiPAZ), 28046 Madrid, Spain.
FAU - Barderas, Rodrigo
AU  - Barderas R
AUID- ORCID: 0000-0003-3539-7469
AD  - Chronic Disease Programme (UFIEC), Instituto de Salud Carlos III, 28220 Madrid, 
      Spain.
LA  - eng
GR  - PI20CIII/00019/Instituto de Salud Carlos III/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231031
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (SPRYD7 protein, human)
SB  - IM
MH  - Humans
MH  - Cell Line, Tumor
MH  - *Colonic Neoplasms
MH  - *Colorectal Neoplasms/pathology
MH  - Phenotype
MH  - Proteomics/methods
PMC - PMC10648221
OTO - NOTNLM
OT  - SPRYD7
OT  - cancer metastasis
OT  - colorectal cancer
OT  - interactome
OT  - protein dysregulation
OT  - proteomics
COIS- The authors declare no conflict of interest.
EDAT- 2023/11/10 12:46
MHDA- 2023/11/13 06:42
PMCR- 2023/10/31
CRDT- 2023/11/10 10:04
PHST- 2023/07/04 00:00 [received]
PHST- 2023/10/12 00:00 [revised]
PHST- 2023/10/24 00:00 [accepted]
PHST- 2023/11/13 06:42 [medline]
PHST- 2023/11/10 12:46 [pubmed]
PHST- 2023/11/10 10:04 [entrez]
PHST- 2023/10/31 00:00 [pmc-release]
AID - cells12212548 [pii]
AID - cells-12-02548 [pii]
AID - 10.3390/cells12212548 [doi]
PST - epublish
SO  - Cells. 2023 Oct 31;12(21):2548. doi: 10.3390/cells12212548.