Lateral Interaction Between CD147 and B7-H3 Determines the Stemness and Survival of Breast Cancer Patients

Oncogenic cell-surface membrane proteins contribute to the phenotypic and functional characteristics of cancer stem cells (CSCs). We quantitatively analyzed cell-surface membrane proteins that are in close proximity to CD147 in CSCs. Moreover, we compared CSCs to non-CSCs to identify CSC-specific cell-surface membrane proteins that are the nearest neighbors of CD147 and revealed that lateral interaction between CD147 and CD276 (B7-H3) concealed within the lipid raft microdomain in CSCs confers resistance to docetaxel. Furthermore, we found that the co-expression of CD147 and CD276 was linked to unfavorable clinical outcome in patients with HER2+ breast cancer receiving chemotherapy (disease-free survival: p = 0.04, METABRIC). Subsequent immunohistochemical analysis indicated that CD147 and CD276 were exclusively associated with an inadequate chemotherapeutic response. Altogether, our data suggest that the lateral interaction between CD147 and its proximal partners may be significantly associated with clinicopathological characteristics and is a critical phenotypic determinant of breast cancer stemness. Funding Information: This research was funded by the National Research Foundation of Korea (NRF) (grant numbers: NRF-2016R1D1A1B04931656 and NRF-2021M3E5D3016636 to K.M.K., NRF-2016R1A5A1010764 and NRF-2020M3E5D9080791 to E.C.Y., and NRF-2017-Global Ph.D. Fellowship Program to J.L.). This research was supported by 2017 Research Grant (No. 520170409) and 2019 Research Grant (PoINT) from Kangwon National University and the BK21 FOUR funded by the Ministry of Education (MOE, Korea) and NRF. Declaration of Interests: The authors declare no competing interests. Ethical Approval: The Institutional Review Board of Seoul National University Hospital approved this study protocol