CDK9 and mTOR: trading places

Borden, Katherine L. B.

doi:10.1182/blood-2019-01-895086

Cited by 3 publications

(3 citation statements)

References 11 publications

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“…CDK9 alongside mTOR complexes modulate translation. TOR complexes have recently emerged as a potential target for autophagic regulation[ 37 ]. This study confirmed that CDK9 is highly expressed in CRC and that expression of CDK9 is positively correlated with autophagy in colon cancer.…”

Section: Discussionmentioning

confidence: 99%

Expression of cyclin-dependent kinase 9 is positively correlated with the autophagy level in colon cancer

Zheng,

Lu,

Kong

2024

World J Gastrointest Oncol

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BACKGROUND Cyclin-dependent kinase 9 (CDK9) expression and autophagy in colorectal cancer (CRC) tissues has not been widely studied. CDK9, a key regulator of transcription, may influence the occurrence and progression of CRC. The expression of autophagy-related genes BECN1 and drug resistance factor ABCG2 may also play a role in CRC. Under normal physiological conditions, autophagy can inhibit tumorigenesis, but once a tumor forms, autophagy may promote tumor growth. Therefore, understanding the relationship between autophagy and cancer, particularly how autophagy promotes tumor growth after its formation, is a key motivation for this research. AIM To investigate the relationship between CDK9 expression and autophagy in CRC, assess differences in autophagy between left and right colon cancer, and analyze the associations of autophagy-related genes with clinical features and prognosis. METHODS We collected tumor tissues and paracarcinoma tissues from colon cancer patients with liver metastasis to observe the level of autophagy in tissues with high levels of CDK9 and low levels of CDK9. We also collected primary tissue from left and right colon cancer patients with liver metastasis to compare the autophagy levels and the expression of BECN1 and ABCG2 in the tumor and paracarcinoma tissues. RESULTS The incidence of autophagy and the expression of BECN1 and ABCG2 were different in left and right colon cancer, and autophagy might be involved in the occurrence of chemotherapy resistance. Further analysis of the relationship between the expression of autophagy-related genes CDK9, ABCG2 , and BECN1 and the clinical features and prognosis of colorectal cancer showed that the high expression of CDK9 indicated a poor prognosis in colorectal cancer. CONCLUSION This study laid the foundation for further research on the combination of CDK9 inhibitors and autophagy inhibitors in the treatment of patients with CRC.

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Section: Discussionmentioning

confidence: 99%

Expression of cyclin-dependent kinase 9 is positively correlated with the autophagy level in colon cancer

Zheng,

Lu,

Kong

2024

World J Gastrointest Oncol

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“…Due to being a part of the major pathways responsible for the development of highly prevalent pathologies, such as cancer, CDK9 represents a new class of pharmaceutical targets. Although CDK9 traditionally acts in transcription elongation, recent studies revealed that it also interacts with a wide range of proteins involved in translation, RNA processing, translation termination, and epigenetic modifications [58,138,139]. Research efforts should continue to elucidate CDK9's functions to understand the higher-order mechanism responsible for the development of malignancies.…”

Section: Future Perspectivesmentioning

confidence: 99%

Targeting cyclin-dependent kinase 9 in cancer therapy

et al. 2021

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Cyclin-dependent kinase (CDK) 9 associates mainly with cyclin T1 and forms the positive transcription elongation factor b (p-TEFb) complex responsible for transcriptional regulation. It has been shown that CDK9 modulates the expression and activity of oncogenes, such as MYC and murine double minute 4 (MDM4), and it also plays an important role in development and/or maintenance of the malignant cell phenotype. Malfunction of CDK9 is frequently observed in numerous cancers. Recent studies have highlighted the function of CDK9 through a variety of mechanisms in cancers, including the formation of new complexes and epigenetic alterations. Due to the importance of CDK9 activation in cancer cells, CDK9 inhibitors have emerged as promising candidates for cancer therapy. Natural product-derived and chemically synthesized CDK9 inhibitors are being examined in preclinical and clinical research. In this review, we summarize the current knowledge on the role of CDK9 in transcriptional regulation, epigenetic regulation, and different cellular factor interactions, focusing on new advances. We show the importance of CDK9 in mediating tumorigenesis and tumor progression. Then, we provide an overview of some CDK9 inhibitors supported by multiple oncologic preclinical and clinical investigations. Finally, we discuss the perspective and challenge of CDK9 modulation in cancer.

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“…The mTOR pathway is involved in cell growth, proliferation, differentiation, apoptosis, and metabolism. [27,28] It is an important target for antitumor therapy because it controls many important aspects of the tumor process. [29,30] Placental development is characterized by extensive angiogenesis.…”

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confidence: 99%

ATL1 inhibits the proliferation and invasion of trophoblast cells via inhibition of the mTOR signaling pathway

Zhang

Feng

Wang

et al. 2022

J Biochem & Molecular Tox

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Pre‐eclampsia (PE) is a major cause of hypertension in maternal and fetal. Atlastin‐1 (ATL1), one regulator of endoplasmic reticulum (ER) morphology, participates in tubular ER formation and protein synthesis. The objective of this study is to investigate the role and molecular mechanism of ATL1 in PE. GEO databases showed that ATL1 was upregulated in PE patients. Our data also found that ATL1 was highly expressed in PE placental tissues. The cell viability, proliferation, migration, and invasion of HTR‐8/SVneo cells increased/decreased after the downregulation/upregulation of ATL1. The mTOR pathway is the downstream pathway of ATL1. The levels of p‐p70S6K and p‐mTOR were increased/decreased after the downregulation/upregulation of ATL1. Moreover, rapamycin, an inhibitor of mTOR pathway, reversed the promotive effect of siATL1 on proliferation, migration, and invasion in HTR‐8/SVneo cells. In conclusion, ATL1 inhibits the proliferation and invasion of trophoblast cells via the inhibition of the mTOR signaling pathway in HTR‐8/SVneo cells.

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CDK9 and mTOR: trading places

Cited by 3 publications

References 11 publications

Expression of cyclin-dependent kinase 9 is positively correlated with the autophagy level in colon cancer

Expression of cyclin-dependent kinase 9 is positively correlated with the autophagy level in colon cancer

Targeting cyclin-dependent kinase 9 in cancer therapy

ATL1 inhibits the proliferation and invasion of trophoblast cells via inhibition of the mTOR signaling pathway

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