Nanog is a promising chemoresistant stemness marker and therapeutic target by iron chelators for esophageal cancer

Toru Narusaka, Toshiaki Ohara, Kazuhiro Noma, Noriyuki Nishiwaki, Yuki Katsura, Takuya Kato, Hiroaki Sato, Yasuko Tomono, Satoru Kikuchi, Hiroshi Tazawa, Yasuhiro Shirakawa, Akihiro Matsukawa, Toshiyoshi Fujiwara

Research output: Contribution to journalArticlepeer-review

Abstract

Esophageal cancer is a disease showing poor prognosis. Although combination chemotherapy using cisplatin (CDDP) and 5-fluorouracil is standard for unresectable esophageal cancer, the response rate is 35%. Cancer stem cells (CSCs) and inflammation are reportedly responsible for the poor prognosis of esophageal cancer. However, comprehensive analyses have not been conducted and proposals for progress remain lacking. Iron is known to be a key factor in the stemness of CSCs. Our study focused on the therapeutic potential of iron control using iron chelators for CSCs in esophageal cancer. Among 134 immunohistochemically analyzed cases, Nanog expression was high in 98 cases and low in 36 cases. High Nanog expression correlated with low overall and disease-free survivals. The iron chelators deferasirox (DFX) and SP10 suppressed the proliferation and expression of stemness markers in TE8 and OE33 cells. DFX and SP10 did not induce compensatory interleukin (IL)-6 secretion, although CDDP did result in high induction. Moreover, BBI608 and SSZ, as other CSC-targeting drugs, could not suppress the expression of stemness markers. Overall, Nanog expression appears related to poor prognosis in esophageal cancer patients, and inhibition of stemness and compensatory IL-6 secretion by iron chelators may offer a novel therapeutic strategy for esophageal cancer.

Original languageEnglish
Pages (from-to)347-357
Number of pages11
JournalInternational Journal of Cancer
Volume149
Issue number2
DOIs
Publication statusPublished - Jul 15 2021
Externally publishedYes

Keywords

  • cancer stem cells
  • chelator
  • esophageal cancer
  • iron
  • stemness

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Nanog is a promising chemoresistant stemness marker and therapeutic target by iron chelators for esophageal cancer'. Together they form a unique fingerprint.

Cite this