Mechanosensitive turnover of phosphoribosyl pyrophosphate synthetases regulates nucleotide metabolism

Li, Jingyi; Shao, Jichun; Zeng, Zhijun; He, Yumin; Tang, Cong; Park, Su Hwan; Lee, Jong-Ho; Li, Rui

doi:10.1038/s41418-021-00851-7

Cited by 6 publications

(8 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 25 Recently, our lab has reported that LATS1/2 phosphorylates and inhibits phosphoribosyl pyrophosphate synthetase, the rate‐limiting enzyme for nucleotide synthesis, thereby impeding DNA and RNA synthesis in response to softened extracellular environment. 9 In this study, we find that STAT3 is a new phosphorylation substrate of MST2. By in vitro kinase assay using [γ‐ 32 P]‐ATP, we show that MST2 recombinant protein, but not MST1, LATS1, LATS2, or kinase‐dead MST2 K56R mutant protein, introduced an autoradiographic signal on STAT3 protein.…”

Section: Discussionmentioning

confidence: 56%

“…Hitherto, accumulating new phosphorylation substrates, functioning in diverse biological processes, have been discovered for Hippo pathway kinases, which largely expand the existing knowledge on the roles of the Hippo pathway in the interconnection with other signaling pathways 25 . Recently, our lab has reported that LATS1/2 phosphorylates and inhibits phosphoribosyl pyrophosphate synthetase, the rate‐limiting enzyme for nucleotide synthesis, thereby impeding DNA and RNA synthesis in response to softened extracellular environment 9 . In this study, we find that STAT3 is a new phosphorylation substrate of MST2.…”

Section: Discussionmentioning

confidence: 99%

“…The Hippo pathway is a conserved signaling pathway across multiple species during evolution that regulates tissue homeostasis and organ development. 8 , 9 Inactivation of the Hippo pathway is frequently observed in tumors due to a variety of mechanisms including mutations and dysregulation of upstream signaling factors. 10 The core kinase cascade, composed by sterile 20‐like kinase 1/2 (MST1/2) and large tumor suppressor 1/2 (LATS1/2), phosphorylates the major downstream effector proteins, Yes‐associated protein (YAP1) and its paralog tafazzin (TAZ), leading to degradation of YAP1 and TAZ or sequestration of these two proteins in cytosol.…”

Section: Introductionmentioning

confidence: 99%

“…The Hippo pathway is a conserved signaling pathway across multiple species during evolution that regulates tissue homeostasis and organ development 8,9 . Inactivation of the Hippo pathway is frequently observed in tumors due to a variety of mechanisms including mutations and dysregulation of upstream signaling factors 10 .…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Hippo pathway monomerizes STAT3 to regulate prostate cancer growth

Tang¹,

Fang

Lai³

et al. 2022

Cancer Science

Self Cite

View full text Add to dashboard Cite

Prostate cancer ranks among the most commonly diagnosed malignancies for men and has become a non‐negligible threat for public health. Interplay between inflammatory factors and cancer cells renders inflammatory tissue environment as a predisposing condition for cancer development. The Hippo pathway is a conserved signaling pathway across multiple species during evolution that regulates tissue homeostasis and organ development. Nevertheless, whether Hippo pathway regulates cancer‐related inflammatory factors remains elusive. Here, we show that high cell density–mediated activation of the Hippo pathway blunts STAT3 activity in prostate cancer cells. Hippo pathway component MST2 kinase phosphorylates STAT3 at T622, which is located in the SH2 domain of STAT3. This phosphorylation blocks the SH2 domain in one STAT3 molecule to bind with the phosphorylated Y705 site in another STAT3 molecule, which further counteracts IL6‐induced STAT3 dimerization and activation. Expression of a nonphosphorylatable STAT3 T622A mutant enhances STAT3 activity and IL6 expression at high cell density and promotes tumor growth in a mice xenograft model. Our findings demonstrate that STAT3 is a novel phosphorylation substrate for MST2 and thereby highlight a regulatory cascade underlying the crosstalk between inflammation and the Hippo pathway in prostate cancer cells.

show abstract

Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Hippo pathway monomerizes STAT3 to regulate prostate cancer growth

Tang¹,

Fang

Lai³

et al. 2022

Cancer Science

Self Cite

View full text Add to dashboard Cite

show abstract

“…5 × 10 6 tumor cells were injected into the back of 6-week-old male BALB/c nude mice. At the indicated time points, the tumor size was measured (volume = 1/2 × length × width 2 ), as previously reported [12].…”

Section: Mouse Tumor Xenograft Modelmentioning

confidence: 99%

IL-6/STAT3 Axis Activates Glut5 to Regulate Fructose Metabolism and Tumorigenesis

Huang¹,

Fang²,

Lai³

et al. 2022

Int. J. Biol. Sci.

Self Cite

View full text Add to dashboard Cite

Cancer cells frequently use fructose as an alternative energy and carbon source, to fuel glycolysis and support the synthesis of various biomacromolecules. Glut5 is the only fructose-specific transporter, which lacks the ability to transport other carbohydrates such as glucose and galactose. Interplay between inflammatory factors and cancer cells renders inflammatory tissue environment as a predisposing condition for cancer development. Nevertheless, how inflammatory factors coordinate with fructose metabolism to facilitate tumor growth remains largely elusive. Here we show that treatment with IL-6 activates fructose uptake and fructolysis in oral squamous cell carcinoma (OSCC) cells and prostate cancer cells. Mechanistic study shows that transcription factor STAT3 associates with Glut5 promoter region and enhances Glut5 transcription in response to IL-6 treatment. Knockdown of Glut5 abolished IL-6-induced fructose uptake and utilization of fructose, and compromises IL-6-elicited tumor cell proliferation. Further, positive correlation between Glut5 and IL-6 expression is observed in multiple cancers. Our findings demonstrate a regulatory cascade underlying the crosstalk between inflammation and fructose metabolism in cancer cells, and highlights Glut5 as a novel oncogenic factor.

show abstract

Extracellular-matrix mechanics regulate cellular metabolism: A ninja warrior behind mechano-chemo signaling crosstalk

Liao

2022

Rev Endocr Metab Disord

View full text Add to dashboard Cite

Mechanosensitive turnover of phosphoribosyl pyrophosphate synthetases regulates nucleotide metabolism

Cited by 6 publications

References 43 publications

Hippo pathway monomerizes STAT3 to regulate prostate cancer growth

Hippo pathway monomerizes STAT3 to regulate prostate cancer growth

IL-6/STAT3 Axis Activates Glut5 to Regulate Fructose Metabolism and Tumorigenesis

Extracellular-matrix mechanics regulate cellular metabolism: A ninja warrior behind mechano-chemo signaling crosstalk

Contact Info

Product

Resources

About