RT Journal Article
SR Electronic
T1 GRP78 regulates CD44v membrane homeostasis and cell spreading in tamoxifen-resistant breast cancer
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900377
DO 10.26508/lsa.201900377
VO 2
IS 4
A1 Tseng, Chun-Chih
A1 Stanciauskas, Ramunas
A1 Zhang, Pu
A1 Woo, Dennis
A1 Wu, Kaijin
A1 Kelly, Kevin
A1 Gill, Parkash S
A1 Yu, Min
A1 Pinaud, Fabien
A1 Lee, Amy S
YR 2019
UL http://www.life-science-alliance.org/content/2/4/e201900377.abstract
AB 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.