Sal‐like protein 4 (SALL4) is overexpressed in breast cancer and might contribute to breast cancer progression, but the molecular mechanism remains unknown. Here, we found that within a group of 371 ethnic Chinese breast cancer patients, SALL4 was associated with lower grade (P = .002) and progesterone receptor positivity (P = .004) for overall cases; lower Ki67 (P = .045) and high vimentin (P = .007) for luminal cases. Patients with high SALL4 expression in lymph node metastasis showed a significantly worse survival than those with low expression. Knockout of SALL4 in a triple‐negative breast cancer cell line MDA‐MB‐231‐Red‐FLuc‐GFP led to suppressed ability in proliferation, clonogenic formation, migration, and mammosphere formation in vitro, tumorigenicity and lung colonization in vivo. On the other hand, overexpression of SALL4 enhanced migration and mammosphere formation in vitro and tumorigenicity in vivo. Mechanistically, there was a positive correlation between SALL4 expression and mesenchymal markers including Zinc finger E‐box binding homeobox 1 (ZEB1), vimentin, Slug, and Snail in vivo. Chromatin immunoprecipitation experiment indicated that SALL4 can bind to the promoter region of vimentin (−778 to −550 bp). Taken together, we hypothesize that SALL4 promotes tumor progression in breast cancer by inducing the mesenchymal markers like vimentin through directly binding to its promoter. Increased SALL4 level in metastatic lymph node relative to the primary site is an important poor survival marker in breast cancer.

中文翻译：

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SALL4通过靶向EMT促进乳腺癌中的肿瘤进展。

Sal样蛋白4（SALL4）在乳腺癌中过表达，可能有助于乳腺癌的进展，但分子机制尚不清楚。在这里，我们发现在371名华裔乳腺癌患者中，SALL4与 总体病例的低年级（P  = .002）和孕激素受体阳性（P = .004）相关。较低的Ki67（P  = .045）和高波形蛋白（P = .007）适用于管腔。淋巴结转移中SALL4表达高的患者生存率明显低于低表达患者。在三阴性乳腺癌细胞系MDA-MB-231-Red-FLuc-GFP中敲除SALL4可抑制体外增殖，克隆形成，迁移和乳球形成，体内致瘤性和肺部定植的能力。另一方面，SALL4的过表达增强了体外迁移和乳球形成以及体内致瘤性。从机理上讲，体内的SALL4表达与包括锌指E-box结合同源异型盒1（ZEB1），波形蛋白，Slug和Snail在内的间质标记之间存在正相关。染色质免疫沉淀实验表明，SALL4可以结合波形蛋白的启动子区域（-778至-550 bp）。在一起 我们假设SALL4通过直接结合其启动子来诱导间质标记物，例如波形蛋白，从而促进乳腺癌的肿瘤进展。相对于原发部位，转移性淋巴结中SALL4水平升高是乳腺癌的重要不良生存标志。