BACH1 Promotes Pancreatic Cancer Metastasis by Repressing Epithelial Genes and Enhancing Epithelial–Mesenchymal Transition

• Published in: Cancer research (Chicago, Ill.) Vol. 80; no. 6; pp. 1279 - 1292
• Main Authors: Sato, Masaki, Matsumoto, Mitsuyo, Saiki, Yuriko, Alam, Mahabub, Nishizawa, Hironari, Rokugo, Masahiro, Brydun, Andrey, Yamada, Shinji, Kaneko, Mika K., Funayama, Ryo, Ito, Mamoru, Kato, Yukinari, Nakayama, Keiko, Unno, Michiaki, Igarashi, Kazuhiko
• Format: Journal Article
• Language: English
• Published: United States 15.03.2020
• ISSN: 0008-5472; 1538-7445; 1538-7445
• DOI: 10.1158/0008-5472.CAN-18-4099

Pancreatic ductal adenocarcinoma (PDAC) is among the cancers with the poorest prognoses due to its highly malignant features. BTB and CNC homology 1 (BACH1) has been implicated in RAS-driven tumor formation. We focused on the role of BACH1 in PDAC, more than 90% of which have mutation. Knockdown of BACH1 in PDAC cell lines reduced cell migration and invasion, in part, by increasing E-cadherin expression, whereas its overexpression showed opposite effects. BACH1 directly repressed the expression of that is known to activate the expression of encoding E-cadherin and to inhibit epithelial-to-mesenchymal transition. BACH1 also directly repressed the expression of genes important for epithelial cell adhesion including and . In a mouse orthotopic implantation model, BACH1 was required for the high metastatic ability of AsPC-1 cells. IHC analysis of clinical specimens with a newly developed anti-BACH1 mAb revealed that high expression of BACH1 is a poor prognostic factor. These results suggest that the gene regulatory network of BACH1 and downstream genes including contribute to the malignant features of PDAC by regulating epithelial-to-mesenchymal transition. SIGNIFICANCE: Greater understanding of the gene regulatory network involved in epithelial-to-mesenchymal transition of pancreatic cancer cells will provide novel therapeutic targets and diagnostic markers.