乳腺癌是最常诊断的恶性肿瘤，并且受益于他莫昔芬等内分泌药物。然而，癌细胞产生耐药性通常会导致复发，从而限制了治疗效果。迫切需要鉴定出可以预测对他莫昔芬反应并识别将从该疗法中临床受益的患者的潜在生物标志物。在这项研究中，我们报告说，XI 型胶原蛋白 α1 (COL11A1) 的高表达与接受他莫昔芬治疗的乳腺癌患者的不良治疗反应和预后相关。为了证实COL11A1在他莫昔芬耐药性发展中的作用，我们建立了稳定表达COL11A1的MCF-7/COL11A1和T47D/COL11A1细胞系。与亲代MCF-7和T47D相比，MCF-7/COL11A1和T47D/COL11A1细胞对4-OHT诱导的生长抑制具有更强的抵抗力。此外，在他莫昔芬耐药的 MCF-7/TamR 和 T47D/TamR 细胞系中，COL11A1 表达水平上调，并且 COL11A1 的耗竭使细胞在体外和体内对 4-OHT 显着敏感。有趣的是，雌激素受体 α (ERα) 表达水平升高，可能是由于 TamR 细胞中 COL11A1 增加所致。此外，COL11A1 的敲除降低了 ERα 及其下游靶基因的表达。总体而言，我们的研究结果表明，过度表达的 COL11A1 会导致他莫昔芬耐药，而靶向 COL11A1 有望逆转内分泌耐药。© 2024。作者。

Breast cancer is the most commonly diagnosed malignancy and benefits from endocrine agents such as tamoxifen. However, the development of drug resistance in cancerous cells often leads to recurrence, thus limiting the therapeutic benefit. Identification of potential biomarkers that can predict response to tamoxifen and recognize patients who will clinically benefit from this therapy is urgently needed. In this study, we report that high collagen type XI alpha 1 (COL11A1) expression was associated with poor therapeutic response and prognosis in breast cancer patients treated with tamoxifen. To confirm the role of COL11A1 in the development of tamoxifen resistance, we established MCF-7/COL11A1 and T47D/COL11A1 cell lines, which stably expressed COL11A1. Compared with parental MCF-7 and T47D, MCF-7/COL11A1 and T47D/COL11A1 cells were more resistant to 4-OHT-induced growth inhibition. Moreover, the level of COL11A1 expression was upregulated in tamoxifen-resistant MCF-7/TamR and T47D/TamR cell lines, and depletion of COL11A1 markedly sensitized the cells to 4-OHT in vitro and in vivo. Interestingly, the level of estrogen receptor α (ERα) expression was elevated, probably due to the increased COL11A1 in TamR cells. In addition, knockdown of COL11A1 decreased the expression of ERα and its downstream target genes. Overall, our findings suggest that overexpressed COL11A1 contributes to tamoxifen resistance, and targeting COL11A1 holds great promise for reversing endocrine resistance.© 2024. The Author(s).