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GRP78 regulates CD44v membrane homeostasis and cell spreading in tamoxifen-resistant breast cancer

GRP78 conducts protein folding and quality control in the ER and shows elevated expression and cell surface translocation in advanced tumors. However, the underlying mechanisms enabling GRP78 to exert novel signaling functions at cell surface are just emerging. CD44 is a transmembrane protein and an...

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Autores principales: Tseng, Chun-Chih, Stanciauskas, Ramunas, Zhang, Pu, Woo, Dennis, Wu, Kaijin, Kelly, Kevin, Gill, Parkash S, Yu, Min, Pinaud, Fabien, Lee, Amy S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Life Science Alliance LLC 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6696983/
https://www.ncbi.nlm.nih.gov/pubmed/31416894
http://dx.doi.org/10.26508/lsa.201900377
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author Tseng, Chun-Chih
Stanciauskas, Ramunas
Zhang, Pu
Woo, Dennis
Wu, Kaijin
Kelly, Kevin
Gill, Parkash S
Yu, Min
Pinaud, Fabien
Lee, Amy S
author_facet Tseng, Chun-Chih
Stanciauskas, Ramunas
Zhang, Pu
Woo, Dennis
Wu, Kaijin
Kelly, Kevin
Gill, Parkash S
Yu, Min
Pinaud, Fabien
Lee, Amy S
author_sort Tseng, Chun-Chih
collection PubMed
description GRP78 conducts protein folding and quality control in the ER and shows elevated expression and cell surface translocation in advanced tumors. However, the underlying mechanisms enabling GRP78 to exert novel signaling functions at cell surface are just emerging. CD44 is a transmembrane protein and an important regulator of cancer metastasis, and isoform switch of CD44 through incorporating additional variable exons to the extracellular juxtamembrane region is frequently observed during cancer progression. Using super-resolution dual-color single-particle tracking, we report that GRP78 interacts with CD44v in plasma membrane nanodomains of breast cancer cells. We further show that targeting cell surface GRP78 by the antibodies can effectively reduce cell surface expression of CD44v and cell spreading of tamoxifen-resistant breast cancer cells. Our results uncover new functions of GRP78 as an interacting partner of CD44v and as a regulator of CD44v membrane homeostasis and cell spreading. This study also provides new insights into anti-CD44 therapy in tamoxifen-resistant breast cancer.
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spelling pubmed-66969832019-08-19 GRP78 regulates CD44v membrane homeostasis and cell spreading in tamoxifen-resistant breast cancer Tseng, Chun-Chih Stanciauskas, Ramunas Zhang, Pu Woo, Dennis Wu, Kaijin Kelly, Kevin Gill, Parkash S Yu, Min Pinaud, Fabien Lee, Amy S Life Sci Alliance Research Articles GRP78 conducts protein folding and quality control in the ER and shows elevated expression and cell surface translocation in advanced tumors. However, the underlying mechanisms enabling GRP78 to exert novel signaling functions at cell surface are just emerging. CD44 is a transmembrane protein and an important regulator of cancer metastasis, and isoform switch of CD44 through incorporating additional variable exons to the extracellular juxtamembrane region is frequently observed during cancer progression. Using super-resolution dual-color single-particle tracking, we report that GRP78 interacts with CD44v in plasma membrane nanodomains of breast cancer cells. We further show that targeting cell surface GRP78 by the antibodies can effectively reduce cell surface expression of CD44v and cell spreading of tamoxifen-resistant breast cancer cells. Our results uncover new functions of GRP78 as an interacting partner of CD44v and as a regulator of CD44v membrane homeostasis and cell spreading. This study also provides new insights into anti-CD44 therapy in tamoxifen-resistant breast cancer. Life Science Alliance LLC 2019-08-15 /pmc/articles/PMC6696983/ /pubmed/31416894 http://dx.doi.org/10.26508/lsa.201900377 Text en © 2019 Tseng et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
Tseng, Chun-Chih
Stanciauskas, Ramunas
Zhang, Pu
Woo, Dennis
Wu, Kaijin
Kelly, Kevin
Gill, Parkash S
Yu, Min
Pinaud, Fabien
Lee, Amy S
GRP78 regulates CD44v membrane homeostasis and cell spreading in tamoxifen-resistant breast cancer
title GRP78 regulates CD44v membrane homeostasis and cell spreading in tamoxifen-resistant breast cancer
title_full GRP78 regulates CD44v membrane homeostasis and cell spreading in tamoxifen-resistant breast cancer
title_fullStr GRP78 regulates CD44v membrane homeostasis and cell spreading in tamoxifen-resistant breast cancer
title_full_unstemmed GRP78 regulates CD44v membrane homeostasis and cell spreading in tamoxifen-resistant breast cancer
title_short GRP78 regulates CD44v membrane homeostasis and cell spreading in tamoxifen-resistant breast cancer
title_sort grp78 regulates cd44v membrane homeostasis and cell spreading in tamoxifen-resistant breast cancer
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6696983/
https://www.ncbi.nlm.nih.gov/pubmed/31416894
http://dx.doi.org/10.26508/lsa.201900377
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