Lee Tae Won, Lee Kyung-Min
Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, Republic of Korea.
Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of Korea.
Anim Cells Syst (Seoul). 2022 Jun 22;26(3):99-107. doi: 10.1080/19768354.2022.2083235. eCollection 2022.
Extracellular matrix protein 1 (ECM1) is associated with a poor prognosis of breast cancers. However, the role of ECM1 with endocrine resistance in estrogen receptor-positive (ER) breast cancers has not been elucidated yet. We show that ECM1 promotes endocrine resistance in ER breast cancers. ECM1 is overexpressed in luminal breast cancer patients compared to the basal type of breast cancer. Significantly, higher expression of ECM1 is associated with poor response to endocrine therapies in luminal B breast cancer patients. We found that ECM1 is upregulated in CAMA1 and MDA-MB-361 cells grown in long-term estrogen-deprived (LTED) conditions. Moreover, the ablation of ECM1 significantly inhibited the proliferation of CAMA1 LTED and MDA-MB-361 LTED cells. Finally, an interrogation of a dataset containing transcriptome and proteome of breast cancer cell lines revealed that the level of mRNA is positively correlated with that of phosphorylated Src. Based on these findings, we strongly suggest that ECM1 significantly contributes to the acquisition of endocrine resistance in ER breast cancers by the activation of Src.
细胞外基质蛋白1（ECM1）与乳腺癌的不良预后相关。然而，ECM1在雌激素受体阳性（ER）乳腺癌的内分泌抵抗中的作用尚未阐明。我们发现ECM1促进ER乳腺癌的内分泌抵抗。与基底型乳腺癌相比，ECM1在管腔型乳腺癌患者中高表达。值得注意的是，ECM1的高表达与管腔B型乳腺癌患者内分泌治疗反应不佳相关。我们发现，在长期雌激素剥夺（LTED）条件下培养的CAMA1和MDA-MB-361细胞中，ECM1上调。此外，敲除ECM1显著抑制CAMA1 LTED和MDA-MB-361 LTED细胞的增殖。最后，对一个包含乳腺癌细胞系转录组和蛋白质组的数据集进行分析发现，mRNA水平与磷酸化Src水平呈正相关。基于这些发现，我们强烈认为ECM1通过激活Src显著促进ER乳腺癌内分泌抵抗的获得。
