Abstract
Triple‐negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis. New treatments improving the survival of TNBC patients are, therefore, urgently required. We performed a transcriptome microarray analysis to identify new treatment targets for TNBC. We found that low‐density lipoprotein receptor‐related protein 8 (LRP8) was more strongly expressed in estrogen receptor‐negative breast tumors, including TNBCs and those overexpressing HER2, than in luminal breast tumors and normal breast tissues. LRP8 depletion decreased cell proliferation more efficiently in estrogen receptor‐negative breast cancer cell lines: TNBC and HER2 overexpressing cell lines. We next focused on TNBC cells for which targeted therapies are not available. LRP8 depletion induced an arrest of the cell cycle progression in G1 phase and programmed cell death. We also found that LRP8 is required for anchorage‐independent growth in vitro, and that its depletion in vivo slowed tumor growth in a xenograft model. Our findings suggest that new approaches targeting LRP8 may constitute promising treatments for hormone‐negative breast cancers, those overexpressing HER2 and TNBCs.
Highlights
Breast cancer is a heterogeneous disease, and its various subtypes can be considered as different diseases, with different clinical outcomes
lipoprotein receptor‐related protein 8 (LRP8) is more expressed in ER−/HER2+ and Triple‐negative breast cancer (TNBC) tumors and that its depletion impairs the viability of ER−/HER2+ and TNBC cells, we focused our study on TNBC for which targeted therapies are not available
We found that a study which was/is not referenced in PubMed showed that LRP8 expression was higher in ER−/HER2− compared to ER+/HER2− tumors, and that LRP8 depletion impaired the proliferation of TNBC cell lines and not in breast cancer cell lines of other types.[21]
Summary
Breast cancer is a heterogeneous disease, and its various subtypes can be considered as different diseases, with different clinical outcomes. Transcriptomic analysis has identified four main breast cancer subtypes: those expressing the estrogen (ER) and/or progesterone (PR) receptors (luminal A and luminal B tumors, the latter being more proliferative), and those not expressing them (basal‐like and ER−/HER2+ tumors, the latter overexpressing human epidermal growth factor receptor 2, HER2).[1,2] Basal‐like tumors are a highly heterogeneous group[3,4,5,6,7] resembling triple‐negative breast cancers (TNBCs), which are characterized by immunohistochemistry (IHC) by their lack of ER/PR expression and. Our results identify LRP8 as a new treatment target in hormone‐negative breast cancers, including ER−/HER2+ and TNBCs, for which new treatments are urgently required due to the high risk of relapse after chemotherapy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
