@article{10902/24658,
year = {2022},
url = {http://hdl.handle.net/10902/24658},
abstract = {Developing mechanistic rationales can improve the clinical management of cutaneous T-cell lymphomas. There is considerable genetic and biological evidence of a malignant network of signaling mechanisms, highly influenced by deregulated TCR/PLC?1 activity, controlling the biology of these lesions. In addition, activated signal transducer and activator of transcription 3 is associated with clinical progression, although the alterations responsible for this have not been fully elucidated. Here, we studied PLC?1-dependent mechanisms that can mediate STAT3 activation and control tumor growth and progression. Downstream of PLC?1, the pharmacological inhibition and genetic knockdown of protein kinase C theta (PKC?) inhibited signal transducer and activator of transcription 3 activation, impaired proliferation, and promoted apoptosis in cutaneous T-cell lymphoma cells. A PKC?-dependent transcriptome in mycosis fungoides/Sézary syndrome cells revealed potential effector genes controlling cytokine signaling, TP53, and actin cytoskeleton dynamics. Consistently, an in vivo chicken embryo model xenografted with mycosis fungoides cells showed that PKC? blockage abrogates tumor growth and spread to distant organs. Finally, the expression of a number of PKC? target genes found in mycosis fungoides cells significantly correlated with that of PRKCQ (PKC?) in 81 human mycosis fungoides samples. In summary, PKC? can play a central role in the activation of malignant cutaneous T-cell lymphoma mechanisms via multiple routes, including, but not restricted to, STAT3. These mechanisms may, in turn, serve as targets for specific therapies.},
organization = {ACKNOWLEDGMENTS: This work has been funded by the Instituto de Salud Carlos III (ISCIII)/FEDER (PI16/00156, PI19/00204, and ASOCIACION LUCHAMOS POR LA VIDA to JPV; PI17/0957 to PLOR). NGD has been supported by a predoctoral contract from UC-IDIVAL. BC holds a RyC contract from MICINN (RYC2018-024004). AEC is funded by ISCIII/MINECO/FEDER (PT17/0009/0019).},
publisher = {Elsevier},
publisher = {J Invest Dermatol
. 2022 May;142(5):1391-1400.e15},
title = {PLCy1/PKC0 Downstream Signaling Controls Cutaneous T-Cell Lymphoma Development and Progression},
author = {García Díaz, Nuria and Casar Martínez, Berta and Alonso-Alonso, Ruth and Quevedo Palacio, Laura and Rodríguez, Marta and Ruso Julve, Fulgencio and Esteve-Codina, Anna and Gut, Marta and Gru, Alejandro A. and González Vela, María del Carmen and Gut, Ivo and Rodriguez-Peralto, José Luis and Varela Egocheaga, Ignacio and Ortiz-Romero, Pablo Luis and Piris, Miguel A. and Vaqué Díez, José Pedro},
}