Artículo
Store-operated calcium entry in breast cancer cells is insensitive to Orai1 and STIM1 N-linked glycosylation
Autor/es | Sánchez-Collado, José
Nieto-Felipe, Joel Jardín, Isaac Bhardwaj, Rajesh Berna-Erro, Alejandro Salido, Ginés M. Smani Hajami, Tarik Rosado, Juan A. |
Departamento | Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica |
Fecha de publicación | 2022-12-29 |
Fecha de depósito | 2023-05-31 |
Publicado en |
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Resumen | N-linked glycosylation is a post-translational modification that affects protein function,
structure, and interaction with other proteins. The store-operated Ca2+ entry (SOCE) core proteins,
Orai1 and STIM1, exhibit ... N-linked glycosylation is a post-translational modification that affects protein function, structure, and interaction with other proteins. The store-operated Ca2+ entry (SOCE) core proteins, Orai1 and STIM1, exhibit N-glycosylation consensus motifs. Abnormal SOCE has been associated to a number of disorders, including cancer, and alterations in Orai1 glycosylation have been related to cancer invasiveness and metastasis. Here we show that treatment of non-tumoral breast epithelial cells with tunicamycin attenuates SOCE. Meanwhile, tunicamycin was without effect on SOCE in luminal MCF7 and triple negative breast cancer (TNBC) MDA-MB-231 cells. Ca2+ imaging experiments revealed that expression of the glycosylation-deficient Orai1 mutant (Orai1N223A) did not alter SOCE in MCF10A, MCF7 and MDA-MB-231 cells. However, expression of the nonglycosylable STIM1 mutant (STIM1N131/171Q) significantly attenuated SOCE in MCF10A cells but was without effect in SOCE in MCF7 and MDA-MB-231 cells. In non-tumoral cells impairment of STIM1 N-linked glycosylation attenuated thapsigargin (TG)-induced caspase-3 activation while in breast cancer cells, which exhibit a smaller caspase-3 activity in response to TG, expression of the non-glycosylable STIM1 mutant (STIM1N131/171Q) was without effect on TG-evoked caspase-3 activation. Summarizing, STIM1 N-linked glycosylation is essential for full SOCE activation in non-tumoral breast epithelial cells; by contrast, SOCE in breast cancer MCF7 and MDA-MB-231 cells is insensitive to Orai1 and STIM1 N-linked glycosylation, and this event might participate in the development of apoptosis resistance. |
Agencias financiadoras | Agencia Estatal de Investigación |
Identificador del proyecto | PID2019-104084GB-C21/AEI/ 10.13039/501100011033
PID2019-104084GB-C22/AEI/10.13039/501100011033 |
Cita | Sánchez-Collado, J., Nieto-Felipe, J., Jardín, I., Bhardwaj, R., Berna-Erro, A., Salido, G.M.,...,Rosado, J.A. (2022). Store-operated calcium entry in breast cancer cells is insensitive to Orai1 and STIM1 N-linked glycosylation. CANCERS, 15 (1), 203. https://doi.org/10.3390/cancers15010203. |
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