PYCR1 knockdown inhibits the proliferation, migration, and invasion by affecting JAK/STAT signaling pathway in lung adenocarcinoma

Gao, Yawen; Luo, Lihua; Xie, Yangchun; Zhao, Yu; Yao, Jie; Liu, Xianling

doi:10.1002/mc.23174

Cited by 42 publications

(31 citation statements)

References 32 publications

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“…Additionally, another reports demonstrated that PYCR1 interference inhibited cell proliferation and enhanced cell apoptosis in hepatocellular carcinoma by repressing JNK/IRS1 pathway (Zhuang et al, 2019). In accord with the study of Yan et al (2019) and Gao et al (2020), our results also showed that PYCR1 could activate JAK/STAT signaling in the BCa cells. Therefore, we are highly convinced that the overexpression of RAC3 activated JAK/STAT signaling through PYCR1 axis.…”

Section: Discussionsupporting

confidence: 90%

“…Furthermore, recent studies have also reported that PYCR1 is up-regulated in human cancers, and thus promote the progression of cancers including non-small-cell lung cancer (Wang et al, 2019), prostate cancer (Zeng et al, 2017), and hepatocellular cancer (Zhuang et al, 2019), among others. Moreover, Yan et al (2019) and Gao et al (2020) demonstrated that the knockdown of PYCR1 inhibits the activation of JAK/STAT signaling in lung adenocarcinoma and colorectal cancers, respectively. Additionally, another reports demonstrated that PYCR1 interference inhibited cell proliferation and enhanced cell apoptosis in hepatocellular carcinoma by repressing JNK/IRS1 pathway (Zhuang et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

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RAC3 Promotes Proliferation, Migration and Invasion via PYCR1/JAK/STAT Signaling in Bladder Cancer

Chen

Song

et al. 2020

Front. Mol. Biosci.

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Background: Bladder cancer (BCa) represents one of the most common malignant cancers with high incidence and mortality rates globally. Dysregulation of gene expression has been shown to play critical roles in cancer progression. RAC3 is up-regulated to play an oncogenic role in several cancers, however, the underlying mechanism of RAC3 in BCa is yet to be elucidated. Therefore, this study aimed to investigate the function and mechanism of RAC3 in BCa. Methods: Bioinformatics analysis was employed to demonstrate the expression of RAC3 and PYCR1 in BCa tissues, as well as, its correlation with the overall survival rate of BCa patients. RT-qPCR was performed to detect and quantify the mRNA levels of RAC3 and PYCR1 in BCa cells and immortalized human bladder epithelial cells. MTT, colony formation and Transwell assays were employed to determine cell proliferation, migration, and invasion. Western blotting was performed to detect and quantity proteins expressed. Results: Bioinformatics analysis showed that RAC3 was up-regulated in BCa tissues when compared to normal tissues. Patients with up-regulated RAC3 expression had lower overall survival than patients with down-regulated RAC3 expression. The mRNA level of RAC3 was higher in BCa cells than in immortalized human bladder epithelial cell. RAC3 promoted cell proliferation, migration, and invasion by activating Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) signaling. Notably, RAC3 up-regulated PYCR1, which is positively correlated with RAC3, and thus played an oncogenic role in BCa cells. Moreover, we demonstrated that RAC3 overexpression activated JAK/STAT signaling via PYCR1 axis. Conclusion: RAC3 promoted cell proliferation, migration, and invasion. This is likely due to its role in activating JAK/STAT signaling, which was mediated by PYCR1. This study provides a novel biomarker and target for diagnostic or therapeutic intervention for BCa.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

RAC3 Promotes Proliferation, Migration and Invasion via PYCR1/JAK/STAT Signaling in Bladder Cancer

Chen

Song

et al. 2020

Front. Mol. Biosci.

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“…Pinch-1, a cell-extracellular adhesion protein, promotes proline biosynthesis by increasing the expression of P5CS (Cui et al 2021 ). Interestingly, SIRT3 regulates proline synthesis by deacetylation of PYCR1 enzyme protein and increasing proline synthesis (Chen et al 2019 ), and knockdown of PYCR1 in lung adenocarcinoma inhibits the proliferation and invasion by modulating JAK/STAT (Gao et al 2020 ). Inhibitors of HDAC induce PRODH transcription and anti-apoptotic autophagy in triple negative breast cancer (Fang et al 2019b ).…”

Section: Proline Metabolism and Cancermentioning

confidence: 99%

Perspectives, past, present and future: the proline cycle/proline-collagen regulatory axis

Phang

2021

Amino Acids

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In the 35 years since the introduction of the “proline cycle”, its relevance to human tumors has been widely established. These connections are based on a variety of mechanisms discovered by many laboratories and have stimulated the search for small molecule inhibitors to treat cancer or metastases. In addition, the multi-layered connections of the proline cycle and the role of proline and hydroxyproline in collagen provide an important regulatory link between the extracellular matrix and metabolism.

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“…Other evidence came from reports showing that overexpressed PYCR1 was associated with poor prognosis [6]. The knockout of PYCR1 is sufficient to impair the in vivo proliferation in ccRCC cancer cells that can be negated by proline addition [5].…”

Section: Proline Starvationmentioning

confidence: 99%

Targeting the Proline–Glutamine–Asparagine–Arginine Metabolic Axis in Amino Acid Starvation Cancer Therapy

et al. 2021

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Proline, glutamine, asparagine, and arginine are conditionally non-essential amino acids that can be produced in our body. However, they are essential for the growth of highly proliferative cells such as cancers. Many cancers express reduced levels of these amino acids and thus require import from the environment. Meanwhile, the biosynthesis of these amino acids is inter-connected but can be intervened individually through the inhibition of key enzymes of the biosynthesis of these amino acids, resulting in amino acid starvation and cell death. Amino acid starvation strategies have been in various stages of clinical applications. Targeting asparagine using asparaginase has been approved for treating acute lymphoblastic leukemia. Targeting glutamine and arginine starvations are in various stages of clinical trials, and targeting proline starvation is in preclinical development. The most important obstacle of these therapies is drug resistance, which is mostly due to reactivation of the key enzymes involved in biosynthesis of the targeted amino acids and reprogramming of compensatory survival pathways via transcriptional, epigenetic, and post-translational mechanisms. Here, we review the interactive regulatory mechanisms that control cellular levels of these amino acids for amino acid starvation therapy and how drug resistance is evolved underlying treatment failure.

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PYCR1 knockdown inhibits the proliferation, migration, and invasion by affecting JAK/STAT signaling pathway in lung adenocarcinoma

Cited by 42 publications

References 32 publications

RAC3 Promotes Proliferation, Migration and Invasion via PYCR1/JAK/STAT Signaling in Bladder Cancer

RAC3 Promotes Proliferation, Migration and Invasion via PYCR1/JAK/STAT Signaling in Bladder Cancer

Perspectives, past, present and future: the proline cycle/proline-collagen regulatory axis

Targeting the Proline–Glutamine–Asparagine–Arginine Metabolic Axis in Amino Acid Starvation Cancer Therapy

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