High glucose microenvironment accelerates tumor growth via SREBP1-autophagy axis in pancreatic cancer.

Abstract

BACKGROUND:

Diabetes is recognized to be a risk factor of pancreatic cancer, but the mechanism has not been fully elucidated. Sterol regulatory element binding protein 1 (SREBP1) is an important transcription factor involved in both lipid metabolism and tumor progression. However, the relationship between high glucose microenvironment, SREBP1 and pancreatic cancer remains to be explored.

METHODS:

Clinical data and surgical specimens were collected. Pancreatic cancer cell lines BxPc-3 and MiaPaCa-2 were cultured in specified medium. Immunohistochemistry (IHC) and western blotting were performed to detect the expression of SREBP1. MTT and colony formation assays were applied to investigate cell proliferation. Immunofluorescence, mRFP-GFP adenoviral vector and transmission electron microscopy were performed to evaluate autophagy. We used streptozotocin (STZ) to establish a high glucose mouse model for the in vivo study.

RESULTS:

We found that high blood glucose levels were associated with poor prognosis in pancreatic cancer patients. SREBP1 was overexpressed in both pancreatic cancer tissues and pancreatic cancer cell lines. High glucose microenvironment promoted tumor proliferation, suppressed apoptosis and inhibited autophagy level by enhancing SREBP1 expression. In addition, activation of autophagy accelerated SREBP1 expression and suppressed apoptosis. Moreover, high glucose promotes tumor growth in vivo by enhancing SREBP1 expression.

CONCLUSION:

Our results indicate that SREBP1-autophagy axis plays a crucial role in tumor progression induced by high glucose microenvironment. SREBP1 may represent a novel target for pancreatic cancer prevention and treatment.

• Authors: Cancan Zhou, Weikun Qian, Jie Li, Jiguang Ma, Xin Chen, Zhengdong Jiang, Liang Cheng, Wanxing Duan, Zheng Wang, Zheng Wu, Qingyong Ma, Xuqi Li
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 38 Issue 1 Pg. 302 (Jul 11 2019) ISSN: 1756-9966 [Electronic] England
• PMID: 31296258 (Publication Type: Journal Article)

Chemical References

• Blood Glucose
• SREBF1 protein, human
• Sterol Regulatory Element Binding Protein 1
• Glucose

Topics

• Adult
• Aged
• Animals
• Apoptosis (genetics)
• Autophagy (genetics)
• Blood Glucose
• Cell Line, Tumor
• Cell Proliferation
• Disease Models, Animal
• Female
• Gene Expression
• Glucose (metabolism)
• Heterografts
• Humans
• Male
• Mice
• Middle Aged
• Models, Biological
• Neoplasm Grading
• Neoplasm Staging
• Pancreatic Neoplasms (genetics, metabolism, mortality, pathology)
• Prognosis
• Sterol Regulatory Element Binding Protein 1 (genetics, metabolism)