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Published on: July 21, 2018
ROCK1 regulates glycolysis in pancreatic cancer via the c-MYC/PFKFB3 pathway
Shuyang Pang1, Yuting Shen1, Yanan Wang1
1School of Life Science and Technology, China Pharmaceutical University, 639, Longmian Avenue, Nanjing, Jiangsu 211198, PR China.
Background:
Dysregulation of Rho-associated coiled coil-containing protein kinases (ROCKs) is involved in the metastasis and progression of various malignant tumors. However, how one of the isomers, ROCK1, regulates glycolysis in tumor cells is incompletely understood. Here, we attempted to elucidate how ROCK1 influences pancreatic cancer (PC) progression by regulating glycolytic activity.
Methods:
The biological function of ROCK1 was analyzed in vitro by establishing a silenced cell model. Coimmunoprecipitation confirmed the direct binding between ROCK1 and c-MYC, and a luciferase reporter assay revealed the binding of c-MYC to the promoter of the PFKFB3 gene. These results were verified in animal experiments.
Results:
ROCK1 was highly expressed in PC tissues and enriched in the cytoplasm, and its high expression was associated with a poor prognosis. Silencing ROCK1 inhibited the proliferation and migration of PC cells and promoted their apoptosis. Mechanistically, ROCK1 directly interacted with c-MYC, promoted its phosphorylation (Ser 62) and suppressed its degradation, thereby increasing the transcription of the key glycolysis regulatory factor PFKFB3, enhancing glycolytic activity and promoting PC growth. Silencing ROCK1 increased gemcitabine (GEM) sensitivity in vivo and in vitro.
Conclusions:
ROCK1 promotes glycolytic activity in PC cells and promotes PC tumor growth through the c-MYC/PFKFB3 signaling pathway. ROCK1 knockdown can inhibit PC tumor growth in vivo and increase the GEM sensitivity of PC tumors, providing a crucial clinical therapeutic strategy for PC.
Insights
Rho-associated coiled coil-containing protein kinase 1 (ROCK1) promotes pancreatic cancer growth by enhancing glycolysis via the c-MYC/PFKFB3 pathway. Inhibiting ROCK1 may offer a new therapeutic strategy for pancreatic cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Dysregulation of Rho-associated coiled coil-containing protein kinases (ROCKs) is implicated in malignant tumor progression.
- The specific role of ROCK1 in regulating glycolysis within tumor cells remains unclear.
- This study investigates ROCK1's influence on pancreatic cancer (PC) progression through glycolytic activity.
Purpose of the Study:
- To elucidate the mechanism by which ROCK1 regulates glycolytic activity in pancreatic cancer cells.
- To determine the potential of targeting ROCK1 as a therapeutic strategy for pancreatic cancer.
Main Methods:
- In vitro analysis using a ROCK1-silenced pancreatic cancer cell model.
- Coimmunoprecipitation and luciferase reporter assays to investigate protein-protein interactions and gene promoter binding.
- In vivo animal experiments to validate findings and assess therapeutic efficacy.
Main Results:
- ROCK1 is highly expressed in PC tissues and associated with poor prognosis.
- ROCK1 silencing inhibited PC cell proliferation and migration, promoting apoptosis.
- ROCK1 directly interacts with c-MYC, stabilizing it and increasing PFKFB3 transcription, thereby enhancing glycolysis and promoting PC growth.
- ROCK1 inhibition increased sensitivity to gemcitabine (GEM) in vitro and in vivo.
Conclusions:
- ROCK1 promotes pancreatic cancer growth by enhancing glycolytic activity via the c-MYC/PFKFB3 signaling pathway.
- ROCK1 knockdown inhibits tumor growth and increases gemcitabine sensitivity in pancreatic cancer.
- Targeting ROCK1 represents a potential clinical therapeutic strategy for pancreatic cancer.
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