RT Journal Article
T1 4F2hc-silencing impairs tumorigenicity of HeLa cells via modulation of galectin-3 and β-catenin signaling, and MMP-2 expression
A1 Santiago-Gómez, Angélica
A1 Barrasa, Juan
A1 Olmo López, Nieves
A1 Lecona, Emilio
A1 Burghardt, Hans
A1 Palacín, Manuel
A1 Lizarbe Iracheta, María Antonia
A1 Turnay Abad, Francisco Javier
AB 4F2hc is a type-II glycoprotein whose covalent-bound association with one of several described light chains yields a heterodimer mainly involved in large neutral amino acid transport. Likewise, it is well known that the heavy chain interacts with β-integrins mediating integrin-dependent events such as survival, proliferation, migration and even transformation. 4F2hc is a ubiquitous protein whose overexpression has been related to tumor development and progression. Stable silencing of 4F2hc in HeLa cells using an artificial miRNA impairs in vivo tumorigenicity and leads to an ineffective proliferation response to mitogens. 4F2hc colocalizes with β1-integrins and CD147, but this interaction does not occur in lipid rafts in HeLa cells. Moreover, silenced cells present defects in integrin- (FAK, Akt and ERK1/2) and hypoxia-dependent signaling, and reduced expression/activity of MMP-2. These alterations seem to be dependent on the inappropriate formation of CD147/4F2hc/β1-integrin heterocomplexes on the cell surface, arising when CD147 cannot interact with 4F2hc. Although extracellular galectin-3 accumulates due to the decrease in MMP-2 activity, galectin-3 signaling events are blocked due to an impaired interaction with 4F2hc, inducing an increased degradation of β-catenin. Furthermore, cell motility is compromised after protein silencing, suggesting that 4F2hc is related to tumor invasion by facilitating cell motility. Therefore, here we propose a molecular mechanism by which 4F2hc participates in tumor progression, favoring first steps of epithelial-mesenchymal transition by inhibition of β-catenin proteasomal degradation through Akt/GSK-3β signaling and enabling cell motility.
PB Elsevier
SN 0167-4889
YR 2013
FD 2013
LK https://hdl.handle.net/20.500.14352/92360
UL https://hdl.handle.net/20.500.14352/92360
LA eng
NO Santiago-Gómez A, Barrasa JI, Olmo N, Lecona E, Burghardt H, Palacín M, Lizarbe MA, Turnay J. Biochim Biophys Acta. 2013 Sep;1833(9):2045-56
NO Ministerio de Ciencia e Innovación (España)
NO Fundación La Maratò
DS Docta Complutense
RD 14 dic 2025