Journal article
Nfe2l1- silenced insulinoma cells acquire aggressiveness and chemoresistance
Endocrine-related cancer, Vol.25(3), pp.185-200
03/2018
DOI: 10.1530/ERC-17-0458
PMID: 29203613
Abstract
The transcription factor nuclear factor erythroid 2-like 1 (NFE2L1 or NRF1) is involved in various critical cell processes such as maintenance of ubiquitin-proteasome system and regulation of the cellular antioxidant response. We previously determined that pancreatic β-cell-specific
-knockout mice had hyperinsulinemia and that silencing of
in mouse islets or MIN6 insulinoma β-cells induced elevated basal insulin release and altered glucose metabolism. Hypoglycemia is a major issue with aggressive insulinomas, although a role of NFE2L1 in this pathology is not defined. In the present work, we studied the tumorigenicity of
deficient insulinoma MIN6 cells (
-KD) and sensitivity to chemotherapy.
-KD cells grew faster and were more aggressive than Scramble cells
In a mouse allograft transplantation model, insulinomas arising from
-KD cells were more aggressive and chemoresistant. The conclusion was amplified using streptozotocin (STZ) administration in an allograft transplantation model in diabetic Akita background mice. Furthermore,
-KD cells were resistant to damage by the chemotherapeutic drugs STZ and 5-fluorouracil, which was linked to binding of hexokinase 1 with mitochondria, enhanced mitochondrial membrane potential and closed mitochondrial potential transition pore. Overall, both
and
data from
-KD insulinoma cells provided evidence of a previously un-appreciated action of NFE2L1 in suppression of tumorigenesis.
silencing desensitizes insulinoma cells and derived tumors to chemotherapeutic-induced damage, likely via metabolic reprograming. These data indicate that NFE2L1 could potentially play an important role in the carcinogenic process and impact chemosensitivity, at least within a subset of pancreatic endocrine tumors.
Details
- Title: Subtitle
- Nfe2l1- silenced insulinoma cells acquire aggressiveness and chemoresistance
- Creators
- Jingqi Fu - China Medical UniversityHongzhi Zheng - China Medical UniversityQi Cui - China Medical UniversityChengjie Chen - China Medical UniversitySimeng Bao - China Medical UniversityJing Sun - China Medical UniversityLu Li - China Medical UniversityBei Yang - China Medical UniversityHuihui Wang - China Medical UniversityYongyong Hou - China Medical UniversityYuanyuan Xu - China Medical UniversityYuanhong Xu - China Medical UniversityQiang Zhang - Emory UniversityJingbo Pi - China Medical University
- Resource Type
- Journal article
- Publication Details
- Endocrine-related cancer, Vol.25(3), pp.185-200
- DOI
- 10.1530/ERC-17-0458
- PMID
- 29203613
- NLM abbreviation
- Endocr Relat Cancer
- ISSN
- 1351-0088
- eISSN
- 1479-6821
- Language
- English
- Date published
- 03/2018
- Academic Unit
- Neurology
- Record Identifier
- 9984302207202771
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