2024-03-29T01:57:06Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1820472022-12-30T11:03:25Zcom_10261_86com_10261_1col_10261_339
PAUF/ZG16B promotes colorectal cancer progression through alterations of the mitotic functions and the Wnt/β-catenin pathway
Escudero-Paniagua, B.
Bartolomé, Rubén Álvaro
Rodríguez, Sandra
Ríos, Vivian de los
Pintado-Berninches, Laura
Jaén, Marta
Lafarga, Miguel
Fernandez-Aceñero, M. Jesús
Casal, J. Ignacio
Ministerio de Economía y Competitividad (España)
Fundación Ramón Areces
Escudero-Paniagua, B. [0000-0003-3882-5529]
Bartolomé, Rubén Álvaro [0000-0002-3292-1491]
de los Ríos, Vivian [0000-0001-5582-6879]
Lafarga, Miguel [0000-0003-3402-1152]
Fernandez-Aceñero, M. Jesús [0000-0002-2439-3553]
Casal, J. Ignacio [0000-0003-1085-2840]
PAUF/ZG16B
Mitosis
Vesicle trafficking
Wnt/ β-catenin
Colorectal cancer progression
37 p.-6 fig.
Pancreatic adenocarcinoma–upregulated factor (PAUF), also known as ZG16B, was previously found in the secretome of metastatic colorectal cancer cells. Here, we demonstrated the presence of PAUF at the intracellular level and its multiple effects on cancer progression. An initial decline of PAUF expression was observed at early stages of colorectal cancer followed by an increase at the metastastic site. PAUF was located at different cellular compartments: membrane-associated vesicles, endosomes, microtubule-associated vesicles, cell growth cones and the cell nucleus. PAUF loss in two colorectal cancer cell lines caused severe alterations in the cell phenotype and cell cycle, including tetraploidy, extensive genomic alterations, micronuclei, and increased apoptosis. An exhaustive analysis of the PAUF interactome using different proteomic approaches revealed the presence of multiple components of the cell cycle, mitotic checkpoint, Wnt pathway and intracellular transport. Among the interacting proteins we found ZW10, a moonlighting protein with a dual function in membrane trafficking and mitosis. In addition, PAUF silencing was associated to APC loss and increased β-catenin nuclear expression. Altogether, our results suggest that PAUF depletion increases aneuploidy, promotes apoptosis and activates the Wnt/β-catenin pathway in colorectal cancer cells facilitating cancer progression. In summary, PAUF behaves as a multifunctional protein, with different roles in cancer progression according to the extra- or intracellular expression, suggesting a therapeutic value for colorectal cancer.
This research was supported by grants from the MINECO (BIO2015-66489-R), Fundación Areces and PRB3 (IPT17/0019 - ISCIII-SGEFI /ERDF).
Peer reviewed
2019-05-22T11:52:21Z
2019-05-22T11:52:21Z
2020-04-22
artículo
http://purl.org/coar/resource_type/c_6501
Carcinogenesis 41 (2) 203-213 (2020)
0143-3334
http://hdl.handle.net/10261/182047
10.1093/carcin/bgz093
1460-2180
http://dx.doi.org/10.13039/100008054
http://dx.doi.org/10.13039/501100003329
en
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BIO2015-66489-R
Publisher's version
https://doi.org/10.1093/carcin/bgz093
Sí
open
Oxford University Press