Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Cancer research (Chicago, Ill.), 2020-03, Vol.80 (6), p.1279-1292

Ort / Verlag

United States

Erscheinungsjahr

2020

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.