SALL4 promotes tumor progression in breast cancer by targeting EMT

Teng Chen, Julia Y.S. Tsang, Xiao Chun Su, Peng Li, Wen Qin Sun, Iris L.K. Wong, Kit Ying Choy, Qing Yang, Gary M.K. Tse, Tak H. Chan (Corresponding Author), Larry M.C. Chow (Corresponding Author)

Research output: Journal article publicationJournal articleAcademic researchpeer-review

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1209-1226
Number of pages18
JournalMolecular Carcinogenesis
Volume59
Issue number10
DOIs
Publication statusPublished - 1 Oct 2020

Keywords

  • breast cancer
  • epithelial-mesenchymal transition
  • lung colonization
  • SALL4
  • tumorigenicity

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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