ROCK2 promotes osteosarcoma growth and metastasis by modifying PFKFB3 ubiquitination and degradation

Deng, Xueqiang; Yao, Xuan; Deng, Jianyong; Zou, Yeqin; Wang, Shanshan; Shan, Wenhao; Liu, Peng; Zhang, Zhibin; Chen, Leifeng; Hao, Lu

doi:10.1016/j.yexcr.2019.111689

Cited by 22 publications

(21 citation statements)

References 33 publications

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“…6phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) is a glycolysis-promoting enzyme catalyzing the conversion between fructose 2,6-bisphosphate and fructose 6-phosphate. ROCK2 interacts with PFKFB3 and attenuates its ubiquitination and degradation in osteosarcoma cells [262]. What's more, glycolysis during different stages of cell cycle in Hela cells is regulated by E3 ligases.…”

Section: Ubiquitination and Metabolic Enzymesmentioning

confidence: 99%

The role of ubiquitination and deubiquitination in cancer metabolism

Sun¹,

Liu²,

Yang³

2020

Mol Cancer

277

178

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Metabolic reprogramming, including enhanced biosynthesis of macromolecules, altered energy metabolism, and maintenance of redox homeostasis, is considered a hallmark of cancer, sustaining cancer cell growth. Multiple signaling pathways, transcription factors and metabolic enzymes participate in the modulation of cancer metabolism and thus, metabolic reprogramming is a highly complex process. Recent studies have observed that ubiquitination and deubiquitination are involved in the regulation of metabolic reprogramming in cancer cells. As one of the most important type of post-translational modifications, ubiquitination is a multistep enzymatic process, involved in diverse cellular biological activities. Dysregulation of ubiquitination and deubiquitination contributes to various disease, including cancer. Here, we discuss the role of ubiquitination and deubiquitination in the regulation of cancer metabolism, which is aimed at highlighting the importance of this post-translational modification in metabolic reprogramming and supporting the development of new therapeutic approaches for cancer treatment.

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Section: Ubiquitination and Metabolic Enzymesmentioning

confidence: 99%

The role of ubiquitination and deubiquitination in cancer metabolism

Sun¹,

Liu²,

Yang³

2020

Mol Cancer

277

178

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“…An EdU assay was performed as previously described. 30 Oxygen Consumption Rate (OCR) and Extracellular Acidification Rate (ECAR)…”

Section: Cell Growth Assaysmentioning

confidence: 99%

ROCK2 Promotes Osteosarcoma Growth and Glycolysis by Up-Regulating HKII via Phospho-PI3K/AKT Signalling

Deng¹,

Deng²,

Yao³

et al. 2021

CMAR

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Background: Osteosarcoma (OS) is a malignant bone tumour that exhibits a high mortality. While tumours thrive in a state of malnutrition, the mechanism by which OS cells adapt to metabolic stress through metabolic reprogramming remains unclear. Methods: We analysed the expression of ROCK2 in osteosarcoma tissues by RT-qPCR and Western blot. Cell proliferation were analysed using CCK8, EdU and colony formation assays. The level of cell glycolysis was detected by glucose-6 phosphate, glucose consumption, lactate production and ATP levels. Results: Herein, our study showed that ROCK2 expression in OS tissues was higher than in adjacent tissues. Functional assays have demonstrated that ROCK2 contributes to the growth of OS cells by inducing aerobic glycolysis. The current study revealed that ROCK2 knockdown decreased the levels of mitochondrial hexokinase II (HKII). And also indicated that ROCK2 served as a key enzyme in glycolysis and that it served an important role in tumour growth. A significant positive correlation was identified between the mRNA and protein expressions of ROCK2 and HKII, further demonstrating that ROCK2-induced glycolysis and proliferation was dependent on HKII expression in OS cells. Mechanistically, ROCK2 promotes HKII expression by activating the phospho-PI3K/AKT signalling pathway. Conclusion:Taken together, the results of the current study linked the two drivers of OS growth and aerobic glycolysis and identified a new mechanism of ROCK2 control in OS.

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“…ROCK2 (Rho associated coiled-coil containing protein kinase 2) upregulation has been described in human glioblastoma CSCs [13], in gastric cancer [14], as well as in ovarian cancer samples [15]. Moreover, ROCK2 expression level has been associated with worse prognosis in osteosarcoma tissues [16]. CTSB (cathepsin-B) overexpression has been identified in several tumors with different effects on patient survival [17].…”

Section: Discussionmentioning

confidence: 99%

Genomic and Epigenomic Profile of Uterine Smooth Muscle Tumors of Uncertain Malignant Potential (STUMPs) Revealed Similarities and Differences with Leiomyomas and Leiomyosarcomas

Conconi

Redaelli

Lissoni

et al. 2021

IJMS

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Uterine smooth muscle tumors of uncertain malignant potential (STUMPs) represent a heterogeneous group of tumors that cannot be histologically diagnosed as unequivocally benign or malignant. For this reason, many authors are working to obtain a better definition of diagnostic and prognostic criteria. In this work, we analyzed the genomic and epigenomic profile of uterine smooth muscle tumors (USMTs) in order to find similarities and differences between STUMPs, leiomyosarcomas (LMSs) and leiomyomas (LMs), and possibly identify prognostic factors in this group of tumors. Array-CGH data on 23 USMTs demonstrated the presence of a more similar genomic profile between STUMPs and LMSs. Some genes, such as PRKDC and PUM2, with a potential prognostic value, were never previously associated with STUMP. The methylation data appears to be very promising, especially with regards to the divergent profile found in the sample that relapsed, characterized by an overall CGI hypomethylation. Finally, the Gene Ontology analysis highlighted some cancer genes that could play a pivotal role in the unexpected aggressive behavior that can be found in some of these tumors. These genes could prove to be prognostic markers in the future.

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ROCK2 promotes osteosarcoma growth and metastasis by modifying PFKFB3 ubiquitination and degradation

Cited by 22 publications

References 33 publications

The role of ubiquitination and deubiquitination in cancer metabolism

The role of ubiquitination and deubiquitination in cancer metabolism

ROCK2 Promotes Osteosarcoma Growth and Glycolysis by Up-Regulating HKII via Phospho-PI3K/AKT Signalling

Genomic and Epigenomic Profile of Uterine Smooth Muscle Tumors of Uncertain Malignant Potential (STUMPs) Revealed Similarities and Differences with Leiomyomas and Leiomyosarcomas

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