2026-04-29T12:24:09Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/158392025-06-13T10:26:40Zcom_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
López-Janeiro, Álvaro
author
Mendes, Marta L
author
Perez-Hernandez, Daniel
author
Echevarría, Irene
author
Ruz-Caracuel, Ignacio
author
Heredia-Soto, Victoria
author
Mendiola, Marta
author
Hardisson, David
author
Argüeso, Pablo
author
Peláez-García, Alberto
author
Guzman-Aranguez, Ana
author
Barderas Manchado, Rodrigo
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Ministerio de Educación, Cultura y Deporte (España)
funder
Consejo Superior de Investigaciones Científicas (España)
funder
Conferencia de Rectores de las Universidades Españolas
2023-04-18T13:20:40Z
2023-04-18T13:20:40Z
2023-02-06
Cell Oncol (Dordr). 2023 Jun;46(3):697-715.
10.1007/s13402-023-00778-w
2211-3436
Cellular oncology (Dordrecht)
36745330
http://hdl.handle.net/20.500.12105/15839
Background: Endometrial cancer (EC) is the most common cancer of the female reproductive organs. Despite the good overall prognosis of most low-grade ECs, FIGO I and FIGO II patients might experience tumor recurrence and worse prognosis. The study of alterations related to EC pathogenesis might help to get insights into underlying mechanisms involved in EC development and progression. Methods: Core tumoral samples were used to investigate the role of C1GALT1 in EC by immunohistochemistry (IHC). ECC-1 cells were used as endometrioid EC model to investigate the effect of C1GALT1 depletion using C1GALT1 specific shRNAs. SILAC quantitative proteomics analyses and cell-based assays, PCR, qPCR, WB, dot-blot and IHC analyses were used to identify, quantify and validate dysregulation of proteins. Results: Low C1GALT1 protein expression levels associate to a more aggressive phenotype of EC. Out of 5208 proteins identified and quantified by LC-MS/MS, 100 proteins showed dysregulation (log2fold-change ≥ 0.58 or ≤-0.58) in the cell protein extracts and 144 in the secretome of C1GALT1 depleted ECC-1 cells. Nine dysregulated proteins were validated. Bioinformatics analyses pointed out to an increase in pathways associated with an aggressive phenotype. This finding was corroborated by loss-of-function cell-based assays demonstrating higher proliferation, invasion, migration, colony formation and angiogenesis capacity in C1GALT1 depleted cells. These effects were associated to the overexpression of ANXA1, as demonstrated by ANXA1 transient silencing cell-based assays, and thus, correlating C1GALT and ANXA1 protein expression and biological effects. Finally, the negative protein expression correlation found by proteomics between C1GALT1 and LGALS3 was confirmed by IHC. Conclusion: C1GALT1 stably depleted ECC-1 cells mimic an EC aggressive phenotype observed in patients and might be useful for the identification and validation of EC markers of progression.
eng
Endometrial cancer
O-glycosylation
C1GALT1
Quantitative proteomics
SILAC
In-depth quantitative proteomics analysis revealed C1GALT1 depletion in ECC-1 cells mimics an aggressive endometrial cancer phenotype observed in cancer patients with low C1GALT1 expression
research article
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In-depthQuantitativeProteomicsAnalysis_2023.pdf
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In-depthQuantitativeProteomicsAnalysis_2023.pdf.txt