Breast Cancer Subtypes Underlying EMT-Mediated Catabolic Metabolism

Cho, Eunae Sandra; Kim, Nam Hee; Yun, Jung Won; Cho, Sue Bean; Kim, Hyun Sil; Yook, Jong In

doi:10.3390/cells9092064

Cited by 23 publications

(14 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous studies reported that EMT is regulated by several signaling pathways, for example Notch-, Wnt-, PI3K/Akt-and NF-kB-dependent pathways (28)(29)(30). Previous studies have confirmed that the EMT enhances tumor cell mobility and invasiveness, thus, contributing to the development of chemotherapy resistance and metastasis (31,32). Additionally, breast cancer recurrence and prognosis have been reported to be affected strongly by EMT (13).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of GLYAT Facilitates Tumor Growth and Metastasis and Poor Clinical Outcomes Through the PI3K/AKT/Snail Pathway in Human Breast Cancer

Tian

Jiang

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

BackgroundThe Glycine N-acyltransferase (GLYAT) gene encodes a protein that catalyzes the transfer of acyl groups from acyl CoA to glycine, resulting in acyl glycine and coenzyme A. Aberrant GLYAT expression is associated with several malignant tumors, but its clinical importance in human breast cancer (BC), has yet to be fully addressed. This study aims to evaluate the clinical function of GLYAT in BC patients.MethodsGLYAT expression was determined by immune blot and immunohistochemistry in three BC cell lines and primary cancer tissues. The MDA-MB 231 cell line was used for GLYAT gene knockdown experiments while the MCF7 cell line for overexpression experiments. Colony formation experiments, soft agar experiments, and transwell assays were utilized for further inspection of cell proliferation and migration capabilities. Immunofluorescence and western blot were used to detect markers of the epithelial-mesenchymal transition (EMT) and changes in the PI3K/AKT/Snail pathway. The role of GLYAT in tumor growth and metastasis was also assessed in nude mice in vivo. Also, a correlation analysis was performed between clinicopathological features and GLYAT expression in BC patients.ResultsGLYAT was decreased in human BC tissues and cell lines. Functional analysis showed that knockdown of GLYAT augmented BC cell proliferation in vitro and in vivo. However, this phenomenon was reversed when GLYAT was overexpressed in the transfected cells. Moreover, downregulation of GLYAT promoted the migratory properties of BC cells, likely through the activation of PI3K/AKT/Snail signaling, which subsequently induced the EMT. IHC analysis indicated that GLYAT was decreased in human BC tissues and lower GLYAT expression was correlated with histological grade, tumor TNM stage, Ki-67 status, and poorer survival in BC patients. Furthermore, lower GLYAT expression seemed as an independent risk factor related to poor prognosis in BC patients based on Cox regression analyses.ConclusionOur findings demonstrate that downregulation of GLYAT expression in human breast cancer is correlated with EMT via the PI3K/AKT/Snail pathway and is also associated with histological grade, tumor TNM stage, Ki-67 status, and poor survival in breast cancer patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Downregulation of GLYAT Facilitates Tumor Growth and Metastasis and Poor Clinical Outcomes Through the PI3K/AKT/Snail Pathway in Human Breast Cancer

Tian

Jiang

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…In particular, it has been found that in luminal A and B subtypes, PFK-1 is downregulated, implying that the glycolytic flux is diverted towards PPP and that, due to the presence of FBP1, gluconeogenesis is active and DHAP and GA3P can be recycled to fuel the PPP. On the contrary, in the basal-like subtype, both FBP1 and ACC2 are downregulated, both glycolysis and PPP have the possibility to be fueled, but in this case, due to the suppression of ACC2, which catalyzes the formation of malonyl-CoA (a strong inhibitor of CPT1), there is a boost towards OXPHOS due to the availability of metabolites from both glycolysis and PPP (DHAP and GA3P) and FAs [ 151 ].…”

Section: Emt and Metabolism In Selected Cancersmentioning

confidence: 99%

The Epithelial–Mesenchymal Transition at the Crossroads between Metabolism and Tumor Progression

Fedele

Sgarra

Battista

et al. 2022

IJMS

View full text Add to dashboard Cite

The transition between epithelial and mesenchymal phenotype is emerging as a key determinant of tumor cell invasion and metastasis. It is a plastic process in which epithelial cells first acquire the ability to invade the extracellular matrix and migrate into the bloodstream via transdifferentiation into mesenchymal cells, a phenomenon known as epithelial–mesenchymal transition (EMT), and then reacquire the epithelial phenotype, the reverse process called mesenchymal–epithelial transition (MET), to colonize a new organ. During all metastatic stages, metabolic changes, which give cancer cells the ability to adapt to increased energy demand and to withstand a hostile new environment, are also important determinants of successful cancer progression. In this review, we describe the complex interaction between EMT and metabolism during tumor progression. First, we outline the main connections between the two processes, with particular emphasis on the role of cancer stem cells and LncRNAs. Then, we focus on some specific cancers, such as breast, lung, and thyroid cancer.

show abstract

“…The invasive growth and metastatic process of cancer cells depends on the epithelial–mesenchymal transition (EMT), a complex biological mechanism. In addition to invasion, EMT in cancer is recently believed to be involved in resistance to cell death, resistance to chemotherapy, immunotherapy and radiation therapy, and stem cell properties [ 3 , 4 , 5 , 6 , 7 ]. It is known that EMT is induced by Snail, a transcriptional repressor of E-cadherin [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Niclosamide and Pyrvinium Are Both Potential Therapeutics for Osteosarcoma, Inhibiting Wnt–Axin2–Snail Cascade

Woo

Hwang

et al. 2021

Cancers

View full text Add to dashboard Cite

Osteosarcoma, the most common primary bone malignancy, is typically related to growth spurts during adolescence. Prognosis is very poor for patients with metastatic or recurrent osteosarcoma, with survival rates of only 20–30%. Epithelial–mesenchymal transition (EMT) is a cellular mechanism that contributes to the invasion and metastasis of cancer cells, and Wnt signaling activates the EMT program by stabilizing Snail and β-catenin in tandem. Although the Wnt/Snail axis is known to play significant roles in the progression of osteosarcoma, and the anthelmintic agents, niclosamide and pyrvinium, have been studied as inhibitors of the Wnt pathway, their therapeutic effects and regulatory mechanisms in osteosarcoma remain unidentified. In this study, we show that both niclosamide and pyrvinium target Axin2, resulting in the suppression of EMT by the inhibition of the Wnt/Snail axis in osteosarcoma cells. Axin2 and Snail are abundant in patient samples and cell lines of osteosarcoma. The treatment of niclosamide and pyrvinium inhibits the migration of osteosarcoma cells at nanomolar concentrations. These results suggest that Axin2 and Snail are candidate therapeutic targets in osteosarcoma, and that anthelminthic agents, niclosamide and pyrvinium, may be effective for osteosarcoma patients.

show abstract

Breast Cancer Subtypes Underlying EMT-Mediated Catabolic Metabolism

Cited by 23 publications

References 73 publications

Downregulation of GLYAT Facilitates Tumor Growth and Metastasis and Poor Clinical Outcomes Through the PI3K/AKT/Snail Pathway in Human Breast Cancer

Downregulation of GLYAT Facilitates Tumor Growth and Metastasis and Poor Clinical Outcomes Through the PI3K/AKT/Snail Pathway in Human Breast Cancer

The Epithelial–Mesenchymal Transition at the Crossroads between Metabolism and Tumor Progression

Niclosamide and Pyrvinium Are Both Potential Therapeutics for Osteosarcoma, Inhibiting Wnt–Axin2–Snail Cascade

Contact Info

Product

Resources

About