Nucleus-located PDK1 regulates growth, invasion and migration of breast cancer cells

Gan, Delu; Yue, Shujun; Jiang, Yulin; Zhang, Dian; Shi, He; Qian, Husun; Zhou, Ting; Fang, Wenli; Yao, Mengli; Zuo, Guo‐Wei; Chen, Tingmei

doi:10.1016/j.lfs.2020.117722

Cited by 9 publications

(8 citation statements)

References 46 publications

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“…PDK1 changes are reported in tumors such as lung, colon, melanoma, and breast. Although the mechanism is unclear, these would appear to be correlated with growth, migration, and metastatic capacity [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Bilateral Phyllodes Giant Tumor. A Case Report Analyzed by Array-CGH

et al. 2020

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The breast phyllodes tumor is a biphasic tumor that accounts for less than of 1% of all breast neoplasms. It is classified as benign, borderline, or malignant, and can mimic benign masses. Some recurrent alterations have been identified. However, a precise molecular classification of these tumors has not yet been established. Herein, we describe a case of a 43-year-old woman that was admitted to the emergency room for a significant bleeding from the breast skin. A voluminous ulcerative mass of the left breast and multiple nodules with micro-calcifications on the right side were detected at a physical examination. A left total mastectomy and a nodulectomy of the right breast was performed. The histological diagnosis of the surgical specimens reported a bilateral giant phyllodes tumor, showing malignant features on the left and borderline characteristics associated with a fibroadenoma on the right. A further molecular analysis was carried out by an array-Comparative Genomic Hybridization (CGH) to characterize copy-number alterations. Many losses were detected in the malignant mass, involving several tumor suppressor genes. These findings could explain the malignant growth and the metastatic risk. In our study, genomic profiling by an array-CGH revealed a greater chromosomal instability in the borderline mass (40 total defects) than in the malignant (19 total defects) giant phyllodes tumor, reflecting the tumor heterogeneity. Should our results be confirmed with more sensitive and specific molecular tests (DNA sequencing and FISH analysis), they could allow a better selection of patients with adverse pathological features, thus optimizing and improving patient’s management.

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Section: Discussionmentioning

confidence: 99%

Bilateral Phyllodes Giant Tumor. A Case Report Analyzed by Array-CGH

et al. 2020

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“…36 In addition, PDK1 interacts with SPRY4-IT1 has been reported in colorectal cancer. 35 And we have found that PDK1 had an obviously nuclear location in breast cancer cells in previous reports, 13 so we wonder that if there is an interaction between PDK1 and SPRY4-IT1 in breast cancer cell. We conducted RIP and RNA pull down assays, the data confirmed our conjecture, PDK1 interacted with SPRY4-IT1 in breast cancer cell (Figure 3C,D).…”

Section: The Knockdown Of Pdk1 Inhibits Breast Cancer Cell Proliferat...mentioning

confidence: 93%

“…A number of evidence have emerged illustrating that PDK1 promotes cell proliferation and inhibits apoptosis in breast cancer. [11][12][13] To explore PDK1 playing a role through 3A). RNA nucleus-cytoplasm isolation experiment showed the same results, 90% SPRY4-IT1 located in nucleus according to our data (Figure 3B).…”

Section: The Knockdown Of Pdk1 Inhibits Breast Cancer Cell Proliferat...mentioning

confidence: 99%

“…12 In our previous research, we demonstrated that PDK1 had a nuclear localization, and nucleus-located PDK1 effectively promoted the proliferation, invasion, and migration of breast cancer cells. 13 Long noncoding RNAs (lncRNAs) are a class of RNAs longer than 200 bases without the ability of coding protein, 14 and have been reported to involve tumor progression by different mechanisms. 15,16 LncRNAs often perform their functions by interacting with proteins, DNA and RNA.…”

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confidence: 99%

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PDK1‐stabilized LncRNA SPRY4‐IT1 promotes breast cancer progression via activating NF‐κB signaling pathway

Zhang

Chen

Yuan

et al. 2023

Molecular Carcinogenesis

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Pyruvate dehydrogenase kinase 1 (PDK1) is a widely known glycolytic enzyme, and some evidence showed that PDK1 promoted breast cancer by multiple approaches. However, very few lncRNAs have been identified to be associated with PDK1 in breast cancer in previous research. In this study, we found that lncRNA sprouty4‐intron transcript 1 (SPRY4‐IT1) was regulated by PDK1 with correlation analysis, and PDK1 upregulated SPRY4‐IT1 remarkably in breast cancer cells, as PDK1 interacted with SPRY4‐IT1 in the nucleus and significantly enhanced the stability of SRPY4‐IT1. Furthermore, SPRY4‐IT1 was highly expressed in breast cancer, significantly promoted the proliferation and inhibited apoptosis of breast cancer cells. In terms of mechanism, SPRY4‐IT1 inhibited the transcription of NFKBIA and the expression of IκBα, thus promoting the formation of p50/p65 complex and activating NF‐κB signaling pathway, which facilitated survival of breast cancer cells. Therefore, our finding reveals that PDK1/SPRY4‐IT1/NFKBIA axis plays a crucial role that promoting tumor progression, and SPRY4‐IT1 knockdown incombined with PDK1 inhibitor is promising to be a new therapeutic strategy in breast cancer.

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“…These findings suggest that inhibition of PDK1 may be a potential strategy for the treatment of EGFR-mediated HNSCC metastasis. Gan et al[76] found that nuclear localized PDK1 promoted breast cancer cell growth, migration and invasion. Zhou[77] reported that in kidney cancer cells, expression ofPDK1 was significantly upregulated and overexpression of miR-375 in A-498 cells inhibited PDK1 via preventing the phosphorylation of AKT.…”

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confidence: 99%

Pyruvate dehydrogenase kinases (PDKs): an overview toward clinical applications

et al. 2021

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Pyruvate dehydrogenase kinase (PDK) can regulate the catalytic activity of pyruvate decarboxylation oxidation via the mitochondrial pyruvate dehydrogenase complex, and it further links glycolysis with the tricarboxylic acid cycle and ATP generation. This review seeks to elucidate the regulation of PDK activity in different species, mainly mammals, and the role of PDK inhibitors in preventing increased blood glucose, reducing injury caused by myocardial ischemia, and inducing apoptosis of tumor cells. Regulations of PDKs expression or activity represent a very promising approach for treatment of metabolic diseases including diabetes, heart failure, and cancer. The future research and development could be more focused on the biochemical understanding of the diseases, which would help understand the cellular energy metabolism and its regulation by pharmacological effectors of PDKs.

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Nucleus-located PDK1 regulates growth, invasion and migration of breast cancer cells

Cited by 9 publications

References 46 publications

Bilateral Phyllodes Giant Tumor. A Case Report Analyzed by Array-CGH

Bilateral Phyllodes Giant Tumor. A Case Report Analyzed by Array-CGH

PDK1‐stabilized LncRNA SPRY4‐IT1 promotes breast cancer progression via activating NF‐κB signaling pathway

Pyruvate dehydrogenase kinases (PDKs): an overview toward clinical applications

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