Expression of CDK13 Was Associated with Prognosis and Expression of HIF-1α and beclin1 in Breast Cancer Patients

Lu, Xiaowei; Zhan, Rui; Zhao, Gansen; Zhen-hua, Qian; Gong, Chan‐Chan; Li, Yanqing

doi:10.1080/08941939.2020.1852344

Cited by 11 publications

(6 citation statements)

References 31 publications

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“…However, to date, no study has discussed the role of HIF-1α in chordoma. In the current study, we detected HIF-1α expression in almost all chordoma samples, which is consistent with previous studies reported in other types of tumors, given that the intracellular hypoxic environment is a universal feature of solid tumors 33,34 . At the same time, we found that HIF-1α was expressed in the cytoplasm or both the cytoplasm and nucleus, which can be explained by the fact that intracellular HIF-1α is generated and accumulates in the cytoplasm and then enters the nucleus to exert its effects.…”

Section: Discussionsupporting

confidence: 93%

“…In the current study, we detected HIF-1α expression in almost all chordoma samples, which is consistent with previous studies reported in other types of tumors, given that the intracellular hypoxic environment is a universal feature of solid tumors. 33,34 At the same time, we found that HIF-1α was expressed in the cytoplasm or both the cytoplasm and nucleus, which can be explained by the fact that intracellular HIF-1α is generated and accumulates in the cytoplasm and then enters the nucleus to exert its effects. Furthermore, our results showed that high HIF-1α expression, tumor invasion, and location of HIF-1α expression were closely related to the prognosis of patients with chordoma, which is consistent with the observations of previous studies.…”

Section: Discussionmentioning

confidence: 93%

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Hypoxia-Inducible Factor-1α (HIF-1α) as a Factor to Predict the Prognosis of Spinal Chordoma

He,

Liu

2024

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Study Design: Retrospective study. Objective: In this study, we explore the potential relationship between HIF-1α and prognosis of patients with spinal chordoma. Summary of Background Data: Currently, prognostic factors related to the clinical course in the setting of spinal chordoma are poorly understood. Although the close relationship between hypoxia inducible factor1α (HIF-1α) and tumor angiogenesis, metastasis and recurrence have been widely reported, it has been not investigated in the context of spinal chordoma. Methods: In this study, 32 samples of chordoma patients were compared to 14 nucleus pulposus tissues as controls. The specific expression of HIF-1α was detected by immunohistochemistry (IHC). Continuous disease-free survival (CDFS) was defined as the interval from tumor resection to confirmation of the first local recurrence or distant metastasis. Overall survival (OS) was defined as the interval from the date of surgery to death related to any cause. The relationship between HIF-1α expression and the clinicopathological characteristics of patients with chordoma was analyzed using Pearson’s chi-square test. Multivariate Cox analysis was used to evaluate whether HIF-1α expression was associated with the prognosis of patients after controlling for confounders. Results: HIF-1α mainly expressed in the cytoplasm or nucleus in all of the chordoma samples which showed significantly higher than that in the normal nucleus pulposus tissue (P=0.004). Multivariate Cox regression analyses showed that high HIF-1α expression and location of HIF-1α expression were significantly associated with poor CDFS (HR=3.374; P=0.021) and OS (HR=4.511; P=0.012). In addition, we further found that high HIF-1α expression both in cytoplasm and nucleus indicated a stronger prognostic factor for poor CDFS (HR=3.885; P=0.011) and OS (HR=4.014; P=0.011) in spinal chordoma patients. Conclusion: High HIF-1α expression may become a potential new biological indicator to predict poor prognosis in patients with spinal chordoma. HIF-1α may also represent a novel therapeutic target for the treatment of spinal chordoma.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 93%

Hypoxia-Inducible Factor-1α (HIF-1α) as a Factor to Predict the Prognosis of Spinal Chordoma

He,

Liu

2024

Spine

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“…In the basal map the frequencies of 155 mutated genes in cluster β also increased with progression of neoplasia ( Figures S12 D and S12F and Table S7 ). The transcriptional regulators and genes controlling cell cycle progression made up the largest group of mutated genes in this cluster consisting of HORMAD1 ( Gao et al., 2018 ), CDK13 ( Lu et al., 2020 ), CDKN2A ( Garcia-Perdomo et al., 2019 ), BTG2 ( Tsui et al., 2018 ), BATF ( Wei et al., 2019 ) among others. In addition to mutational change, CDKN2A is frequently inactivated in many cancers including bladder cancers via homozygous deletions and methylation ( Garcia-Perdomo et al., 2019 ).…”

Section: Resultsmentioning

confidence: 99%

The origin of bladder cancer from mucosal field effects

et al. 2022

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“…CDK1 has been identified as a clinically useful prognostic marker in non‐small cell lung cancer, colon cancer, and breast cancer 52–55 . Apart from CDK1 other CDKs like CDK12 and CDK13 are also deregulated in different cancer, including GC, 56–58 and are reported as therapeutic targets in Triple‐Negative Breast Cancer 59 …”

Section: Discussionmentioning

confidence: 99%

Hyperactivation of MEK/ERK pathway by Ca²⁺/calmodulin‐dependent protein kinase kinase 2 promotes cellular proliferation by activating cyclin‐dependent kinases and minichromosome maintenance protein in gastric cancer cells

Najar

Aravind

Dagamajalu

et al. 2021

Molecular Carcinogenesis

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Although CAMKK2 is overexpressed in several cancers, its role and relevant downstream signaling pathways in gastric cancer (GC) are poorly understood. Treatment of AGS GC cells with a CAMKK2 inhibitor, STO‐609, resulted in decreased cell proliferation, cell migration, invasion, colony‐forming ability, and G1/S‐phase arrest. Quantitative phosphoproteomics in AGS cells with the CAMKK2 inhibitor led to the identification of 9603 unique phosphosites mapping to 3120 proteins. We observed decreased phosphorylation of 1101 phosphopeptides (1.5‐fold) corresponding to 752 proteins upon CAMKK2 inhibition. Bioinformatics analysis of hypo‐phosphorylated proteins revealed enrichment of MAPK1/MAPK3 signaling. Kinase enrichment analysis of hypo‐phosphorylated proteins using the X2K Web tool identified ERK1, cyclin‐dependant kinase 1 (CDK1), and CDK2 as downstream substrates of CAMKK2. Moreover, inhibition of CAMKK2 and MEK1 resulted in decreased phosphorylation of ERK1, CDK1, MCM2, and MCM3. Immunofluorescence results were in concordance with our mass spectroscopy data and Western blot analysis results. Taken together, our data reveal the essential role of CAMKK2 in the pathobiology of GC through the activation of the MEK/ERK1 signaling cascade.

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Expression of CDK13 Was Associated with Prognosis and Expression of HIF-1α and beclin1 in Breast Cancer Patients

Cited by 11 publications

References 31 publications

Hypoxia-Inducible Factor-1α (HIF-1α) as a Factor to Predict the Prognosis of Spinal Chordoma

Hypoxia-Inducible Factor-1α (HIF-1α) as a Factor to Predict the Prognosis of Spinal Chordoma

The origin of bladder cancer from mucosal field effects

Hyperactivation of MEK/ERK pathway by Ca²⁺/calmodulin‐dependent protein kinase kinase 2 promotes cellular proliferation by activating cyclin‐dependent kinases and minichromosome maintenance protein in gastric cancer cells

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Expression of CDK13 Was Associated with Prognosis and Expression of HIF-1α and beclin1 in Breast Cancer Patients

Cited by 11 publications

References 31 publications

Hypoxia-Inducible Factor-1α (HIF-1α) as a Factor to Predict the Prognosis of Spinal Chordoma

Hypoxia-Inducible Factor-1α (HIF-1α) as a Factor to Predict the Prognosis of Spinal Chordoma

The origin of bladder cancer from mucosal field effects

Hyperactivation of MEK/ERK pathway by Ca2+/calmodulin‐dependent protein kinase kinase 2 promotes cellular proliferation by activating cyclin‐dependent kinases and minichromosome maintenance protein in gastric cancer cells

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Hyperactivation of MEK/ERK pathway by Ca²⁺/calmodulin‐dependent protein kinase kinase 2 promotes cellular proliferation by activating cyclin‐dependent kinases and minichromosome maintenance protein in gastric cancer cells