TY - JOUR
T1 - Polarity protein SCRIB interacts with SLC3A2 to regulate proliferation and tamoxifen resistance in ER+ breast cancer
AU - Saito, Yasuhiro
AU - Matsuda, Shiori
AU - Ohnishi, Naomi
AU - Endo, Keiko
AU - Ashitani, Sanae
AU - Ohishi, Maki
AU - Ueno, Ayano
AU - Tomita, Masaru
AU - Ueda, Koji
AU - Soga, Tomoyoshi
AU - Muthuswamy, Senthil K.
N1 - Funding Information:
We thank members of the Soga laboratory for the discussion. Funding supported this work from a Grant-in-Aid for Scientific Research (C) and Grant-in-Aid for Research Activity Start-up from the Japan Society for the Promotion of Science (JSPS), The Mochida Memorial Foundation, The Yasuda Medical Foundation, Astellas Foundation for Research on Metabolic Disorders, Kanae Foundation, The Uehara Memorial Foundation, and The Naito Foundation (Y.S.) and the foundation from Yamagata prefectural government and the City of Tsuruoka (Y.S., S.M., K.E., S.A., M.O., A.U., M.T., and T.S.). S.K.M was supported by a grant from the Breast Cancer Research Foundation.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Estrogen receptor (ER) positive breast cancer represents 75% of all breast cancers in women. Although patients with ER+ cancers receive endocrine therapies, more than 30% develop resistance and succumb to the disease, highlighting the need to understand endocrine resistance. Here we show an unexpected role for the cell polarity protein SCRIB as a tumor-promoter and a regulator of endocrine resistance in ER-positive breast cancer cells. SCRIB expression is induced by estrogen signaling in a MYC-dependent manner. SCRIB interacts with SLC3A2, a heteromeric component of leucine amino acid transporter SLC7A5. SLC3A2 binds to the N-terminus of SCRIB to facilitate the formation of SCRIB/SLC3A2/LLGL2/SLC7A5 quaternary complex required for membrane localization of the amino acid transporter complex. Both SCRIB and SLC3A2 are required for cell proliferation and tamoxifen resistance in ER+ cells identifying a new role for the SCRIB/SLC3A2 complex in ER+ breast cancer.
AB - Estrogen receptor (ER) positive breast cancer represents 75% of all breast cancers in women. Although patients with ER+ cancers receive endocrine therapies, more than 30% develop resistance and succumb to the disease, highlighting the need to understand endocrine resistance. Here we show an unexpected role for the cell polarity protein SCRIB as a tumor-promoter and a regulator of endocrine resistance in ER-positive breast cancer cells. SCRIB expression is induced by estrogen signaling in a MYC-dependent manner. SCRIB interacts with SLC3A2, a heteromeric component of leucine amino acid transporter SLC7A5. SLC3A2 binds to the N-terminus of SCRIB to facilitate the formation of SCRIB/SLC3A2/LLGL2/SLC7A5 quaternary complex required for membrane localization of the amino acid transporter complex. Both SCRIB and SLC3A2 are required for cell proliferation and tamoxifen resistance in ER+ cells identifying a new role for the SCRIB/SLC3A2 complex in ER+ breast cancer.
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U2 - 10.1038/s42003-022-03363-3
DO - 10.1038/s42003-022-03363-3
M3 - Article
C2 - 35501367
AN - SCOPUS:85129269345
SN - 2399-3642
VL - 5
JO - Communications biology
JF - Communications biology
IS - 1
M1 - 403
ER -
