Yadav Sushma, Kowolik Claudia M, Schmolze Daniel, Yuan Yuan, Lin Min, Riggs Arthur D, Horne David A
Department of Cancer Biology and Molecular Medicine, City of Hope National Medical Center, Duarte, CA 91010, USA.
Diabetes and Metabolism Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
Cells. 2025 Jan 17;14(2):128. doi: 10.3390/cells14020128.
Structural maintenance of chromosome-1A (SMC1A) is overexpressed in various malignancies including triple-negative breast cancer (TNBC). As a core component of the cohesin complex, SMC1A was initially recognized for its involvement in chromosomal cohesion and DNA-repair pathways. However, recent studies have unveiled its pivotal role in epithelial-mesenchymal transition (EMT), metastasis, and chemo- and radio-resistance in cancer cells. In hepatocellular carcinoma, aberrant phosphorylation of SMC1A has been associated with enhanced cell proliferation and migration. Despite these insights, the precise role of SMC1A phosphorylation in breast cancer remains largely unexplored. This study represents the first investigation to test the phosphorylation status and subcellular localization of SMC1A (p-SMC1A) in breast cancer and normal breast tissues. Immunohistochemical (IHC) staining was conducted using previously validated phospho-SMC1A antibodies on a histological section and tissue microarray (TMA) comprising samples from primary, invasive, and metastatic breast cancer and normal breast tissues. Our results revealed that p-SMC1A staining intensity was lower in normal breast tissues compared to invasive or metastatic breast cancer tissues ( < 0.001). Approximately 40% of breast cancer tissue exhibited cytoplasmic/membranous localization of p-SMC1A, whereas nuclear expression was observed in normal breast tissues. Moreover, elevated phosphorylation levels were significantly associated with higher tumor grade and metastasis.
染色体结构维持蛋白1A（SMC1A）在包括三阴性乳腺癌（TNBC）在内的多种恶性肿瘤中过表达。作为黏连蛋白复合体的核心成分，SMC1A最初因其参与染色体黏连和DNA修复途径而被认识。然而，最近的研究揭示了其在癌细胞上皮-间质转化（EMT）、转移以及化疗和放疗抗性中的关键作用。在肝细胞癌中，SMC1A的异常磷酸化与细胞增殖和迁移增强有关。尽管有这些发现，但SMC1A磷酸化在乳腺癌中的精确作用仍 largely未被探索。本研究是首次检测SMC1A（p-SMC1A）在乳腺癌和正常乳腺组织中的磷酸化状态和亚细胞定位的研究。使用先前验证的磷酸化SMC1A抗体对包含原发性、浸润性和转移性乳腺癌及正常乳腺组织样本的组织切片和组织芯片（TMA）进行免疫组织化学（IHC）染色。我们的结果显示，与浸润性或转移性乳腺癌组织相比，正常乳腺组织中p-SMC1A染色强度较低（<0.001）。约40%的乳腺癌组织表现出p-SMC1A的细胞质/膜定位，而在正常乳腺组织中观察到核表达。此外，磷酸化水平升高与更高的肿瘤分级和转移显著相关。
