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Published on: June 12, 2017
Decreased expression of GRIM-19 induces autophagy through the AMPK/ULK1 signaling pathway during adenomyosis†
YuFei Huang1, Yue Zhao1, HaoRan Liu1
1Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, P. R. China.
Abstract:
The processes underlying adenomyosis are similar to those of tumor metastasis, and it is defined as progressive invasion by the endometrium and the subsequent creation of ectopic lesions. GRIM-19 regulates cell death via the mitochondrial respiratory chain. Stress following oxygen deprivation can induce tumor cell autophagy, leading to cell invasion and migration. Here, we revealed that GRIM-19 negatively regulates autophagy, and, at least in adenomyosis, decreased expression of GRIM-19 is accompanied by an increased level of autophagy and 5'-adenosine monophosphate-activated protein kinase-Unc-51 like autophagy activating kinase 1 (AMPK-ULK1) activation. Upregulation of GRIM-19 expression in human primary endometrial cells and ISHIKAWA cells inhibits autophagy via the AMPK-ULK1 pathway and helps control cell invasion and migration. In addition, we also identified increased expression of AMPK and ULK1, and higher levels of autophagy in the uterine tissues of GRIM-19+/- mice. Importantly, the function of the GRIM-19-AMPK-ULK1 axis in regulating autophagy in adenomyosis is similar to that of tumor tissues, which may help elucidate the regulation of adenomyosis tumor-like behavior, and is expected to help identify novel targets for the diagnosis and treatment of adenomyosis.
Insights
GRIM-19 protein inhibits autophagy, a process linked to tumor metastasis. Decreased GRIM-19 in adenomyosis increases autophagy and cell invasion, suggesting a new therapeutic target for this condition.
Area of Science:
- Cell Biology
- Oncology
- Gynecology
Background:
- Adenomyosis involves endometrial invasion, similar to tumor metastasis.
- GRIM-19 is a protein regulating cell death through the mitochondrial respiratory chain.
- Cellular stress, like oxygen deprivation, can trigger autophagy, promoting tumor cell invasion and migration.
Purpose of the Study:
- To investigate the role of GRIM-19 in regulating autophagy in adenomyosis.
- To explore the relationship between GRIM-19 expression, autophagy, and cell invasion in adenomyosis.
- To determine if the GRIM-19-AMPK-ULK1 pathway in adenomyosis mirrors its function in tumor tissues.
Main Methods:
- Investigated GRIM-19's effect on autophagy in human endometrial and ISHIKAWA cells.
- Analyzed the activation of the 5'-adenosine monophosphate-activated protein kinase-Unc-51 like autophagy activating kinase 1 (AMPK-ULK1) pathway.
- Examined GRIM-19, AMPK, ULK1 expression, and autophagy levels in GRIM-19+/- mouse uterine tissues.
Main Results:
- GRIM-19 negatively regulates autophagy.
- Decreased GRIM-19 expression in adenomyosis correlates with increased autophagy and AMPK-ULK1 activation.
- Upregulating GRIM-19 inhibits autophagy and reduces cell invasion and migration.
- GRIM-19+/- mice showed increased AMPK, ULK1, and autophagy in uterine tissues.
Conclusions:
- The GRIM-19-AMPK-ULK1 axis plays a crucial role in regulating autophagy in adenomyosis.
- Adenomyosis exhibits tumor-like behavior regulated by autophagy, similar to tumor tissues.
- This pathway presents a potential target for novel adenomyosis diagnosis and treatment strategies.
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