Inhibition of RPS6K reveals context-dependent Akt activity in luminal breast cancer cells.

Aberrant signaling through insulin (Ins) and insulin-like growth factor I (IGF1) receptors contribute to the risk and advancement of many cancer types by activating cell survival cascades. Similarities between these pathways have thus far prevented the development of pharmacological interventions th...

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Autores principales:	Cemal Erdem, Adrian V Lee, D Lansing Taylor, Timothy R Lezon
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/5a50932ee04e4320af6e668981cb0eb3
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spelling	oai:doaj.org-article:5a50932ee04e4320af6e668981cb0eb32021-11-25T05:40:33ZInhibition of RPS6K reveals context-dependent Akt activity in luminal breast cancer cells.1553-734X1553-735810.1371/journal.pcbi.1009125https://doaj.org/article/5a50932ee04e4320af6e668981cb0eb32021-06-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009125https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Aberrant signaling through insulin (Ins) and insulin-like growth factor I (IGF1) receptors contribute to the risk and advancement of many cancer types by activating cell survival cascades. Similarities between these pathways have thus far prevented the development of pharmacological interventions that specifically target either Ins or IGF1 signaling. To identify differences in early Ins and IGF1 signaling mechanisms, we developed a dual receptor (IGF1R & InsR) computational response model. The model suggested that ribosomal protein S6 kinase (RPS6K) plays a critical role in regulating MAPK and Akt activation levels in response to Ins and IGF1 stimulation. As predicted, perturbing RPS6K kinase activity led to an increased Akt activation with Ins stimulation compared to IGF1 stimulation. Being able to discern differential downstream signaling, we can explore improved anti-IGF1R cancer therapies by eliminating the emergence of compensation mechanisms without disrupting InsR signaling.Cemal ErdemAdrian V LeeD Lansing TaylorTimothy R LezonPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 6, p e1009125 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Cemal Erdem Adrian V Lee D Lansing Taylor Timothy R Lezon Inhibition of RPS6K reveals context-dependent Akt activity in luminal breast cancer cells.
description	Aberrant signaling through insulin (Ins) and insulin-like growth factor I (IGF1) receptors contribute to the risk and advancement of many cancer types by activating cell survival cascades. Similarities between these pathways have thus far prevented the development of pharmacological interventions that specifically target either Ins or IGF1 signaling. To identify differences in early Ins and IGF1 signaling mechanisms, we developed a dual receptor (IGF1R & InsR) computational response model. The model suggested that ribosomal protein S6 kinase (RPS6K) plays a critical role in regulating MAPK and Akt activation levels in response to Ins and IGF1 stimulation. As predicted, perturbing RPS6K kinase activity led to an increased Akt activation with Ins stimulation compared to IGF1 stimulation. Being able to discern differential downstream signaling, we can explore improved anti-IGF1R cancer therapies by eliminating the emergence of compensation mechanisms without disrupting InsR signaling.
format	article
author	Cemal Erdem Adrian V Lee D Lansing Taylor Timothy R Lezon
author_facet	Cemal Erdem Adrian V Lee D Lansing Taylor Timothy R Lezon
author_sort	Cemal Erdem
title	Inhibition of RPS6K reveals context-dependent Akt activity in luminal breast cancer cells.
title_short	Inhibition of RPS6K reveals context-dependent Akt activity in luminal breast cancer cells.
title_full	Inhibition of RPS6K reveals context-dependent Akt activity in luminal breast cancer cells.
title_fullStr	Inhibition of RPS6K reveals context-dependent Akt activity in luminal breast cancer cells.
title_full_unstemmed	Inhibition of RPS6K reveals context-dependent Akt activity in luminal breast cancer cells.
title_sort	inhibition of rps6k reveals context-dependent akt activity in luminal breast cancer cells.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/5a50932ee04e4320af6e668981cb0eb3
work_keys_str_mv	AT cemalerdem inhibitionofrps6krevealscontextdependentaktactivityinluminalbreastcancercells AT adrianvlee inhibitionofrps6krevealscontextdependentaktactivityinluminalbreastcancercells AT dlansingtaylor inhibitionofrps6krevealscontextdependentaktactivityinluminalbreastcancercells AT timothyrlezon inhibitionofrps6krevealscontextdependentaktactivityinluminalbreastcancercells
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Inhibition of RPS6K reveals context-dependent Akt activity in luminal breast cancer cells.

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