The CAS Key Laboratory of Innate Immunity and Chronic Disease, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Science and Medical Center, University of Science & Technology of China, Hefei, Anhui, 230027, China.
Key Laboratory of Breast Cancer in Shanghai, Cancer Institute, Department of Breast Surgery; Institutes of Biomedical Sciences; Innovation Center for Cell Signaling Network; Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Cell Death Dis. 2018 Jan 26;9(2):126. doi: 10.1038/s41419-017-0143-z.
Annexin A3 (ANXA3) is dysregulated and plays an important role in various cancers. However, the role of ANXA3 in breast cancer is still unclear. Here, we observed that the expression level of ANXA3 was significantly upregulated in breast cancer tissues. ANXA3 knockdown inhibited cell invasion but promoted cell proliferation in both in vitro and in vivo assays. Furthermore, we found that ANXA3 knockdown inhibited the NFκB pathway via upregulating IκBα, resulting in mesenchymal-epithelial transition (MET) and a heterogeneity change of breast cancer stem cells (BCSCs). In addition, we demonstrated that ANXA3 knockdown increased the sensitivity of breast cancer cells to doxorubicin by increasing the drug uptake. The combination of ANXA3 knockdown and doxorubicin treatment simultaneously inhibited tumor growth and metastasis in vivo. This study described the role and mechanisms of ANXA3 in regulating BCSCs and breast cancer growth and metastasis, indicating that downregulating ANXA3 together with chemotherapy might be a novel therapeutic strategy for treating breast cancer.
膜联蛋白 A3（ANXA3）失调并在各种癌症中发挥重要作用。然而，ANXA3 在乳腺癌中的作用尚不清楚。在这里，我们观察到 ANXA3 的表达水平在乳腺癌组织中显著上调。ANXA3 敲低抑制了体外和体内实验中细胞的侵袭，但促进了细胞的增殖。此外，我们发现 ANXA3 敲低通过上调 IκBα 抑制 NFκB 通路，导致间充质-上皮转化（MET）和乳腺癌干细胞（BCSCs）的异质性改变。此外，我们证明 ANXA3 敲低通过增加药物摄取增加了乳腺癌细胞对阿霉素的敏感性。ANXA3 敲低和阿霉素联合治疗同时抑制了体内肿瘤的生长和转移。这项研究描述了 ANXA3 在调节 BCSCs 和乳腺癌生长和转移中的作用和机制，表明与化疗一起下调 ANXA3 可能是治疗乳腺癌的一种新的治疗策略。
