Downregulation of c-MYC Protein Levels Contributes to Cancer Cell Survival under Dual Deficiency of Oxygen and Glucose

Okuyama, Hiroaki; Endo, Hideki; Akashika, Tamaki; Kato, Kikuya; Inoue, Masahiro

doi:10.1158/0008-5472.can-10-2720

Cited by 89 publications

(96 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…MYC increases expression of vascular endothelial growth factor [227] and decreases the expression of thrombospondin-1 [228] to trip the "angiogenic switch"-that point in tumor development where events align to allow nascent tumor masses to develop their own vasculature. MYC protein stability is fine-tuned to allow tumor cells that are distant from the nutrient and oxygen supply of blood vessels to decrease their MYC levels, avoiding the inevitable death that would occur as a result of nutrient deficiency in the core of the tumor mass [229]. In models of pancreatic cancer development, forced expression of MYC in -cells leads to release of the inflammatory cytokine interleukin-, which in turn coaxes adjacent endothelial cells to proliferate and form the vascular network [230], a function further stimulated by MYC-dependent activation of inflammatory responses that lead to stromal remodeling [231].…”

Section: Influencing the Tumor Environmentmentioning

confidence: 99%

Mammalian MYC Proteins and Cancer

Tansey

2014

New Journal of Science

135

160

View full text Add to dashboard Cite

The MYC family of proteins is a group of basic-helix-loop-helix-leucine zipper transcription factors that feature prominently in cancer. Overexpression of MYC is observed in the vast majority of human malignancies and promotes an extraordinary set of changes that impact cell proliferation, growth, metabolism, DNA replication, cell cycle progression, cell adhesion, differentiation, and metastasis. The purpose of this review is to introduce the reader to the mammalian family of MYC proteins, highlight important functional properties that endow them with their potent oncogenic potential, describe their mechanisms of action and of deregulation in cancer cells, and discuss efforts to target the unique properties of MYC, and of MYC-driven tumors, to treat cancer.

show abstract

Section: Influencing the Tumor Environmentmentioning

confidence: 99%

Mammalian MYC Proteins and Cancer

Tansey

2014

New Journal of Science

135

160

View full text Add to dashboard Cite

show abstract

“…The MYC proto-oncogene protein (hereafter MYC) serves key roles in the proliferation (7), cell cycle (8), differentiation and apoptosis of cells (9,10). However, abnormal expression of MYC has been implicated in almost all human tumors (11).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of MYC binding protein promotes invasion and migration in gastric cancer

et al. 2018

View full text Add to dashboard Cite

Abstract. Gastric cancer (GC) is the second leading cause of cancer-associated mortality worldwide. Although the mortality rate of patients with GC has improved, it remains a significant health issue. The MYC proto-oncogene protein serves key roles in cellular proliferation, differentiation, transformation and apoptosis. Previous studies have identified the abnormal expression of MYC-binding protein (MYCBP) during tumorigenesis in multiple types of cancer. Furthermore, evidence demonstrates that the abnormal expression of MYCBP contributes to the invasion and migration of human cancer types, including colon cancer and glioma; however, its influence on GC remains unclear. In the present study, the expression of MYCBP in GC cells and tissues was analyzed by reverse transcription-quantitative polymerase chain reaction. Additionally, GC cell lines were transfected with small interfering RNAs against MYCBP or lymphoid enhancer-binding factor 1 (LEF-1) and assessed by in vitro transwell migration and invasion assays. The results indicated that the expression of MYCBP in GC cells and tissues was markedly increased compared with a normal gastric epithelial cell line and adjacent normal gastric mucosal tissues, respectively. Furthermore, MYCBP downregulation notably inhibited the metastatic capacity of GC cells, and LEF-1 knockdown was found to downregulate the expression of MYCBP. On the basis of the findings of the present study, MYCBP may be a direct target of the β-catenin/LEF-1 pathway via binding LEF-1, and could potentially be used as a biomarker for the diagnosis and prognosis of GC.

show abstract

“…11A and B). c-Myc protein expression has been detected in the tumor area proximal to the blood vessels (moderate hypoxia), but no c-Myc was detected in the tumor area distant from blood vessels (severe hypoxia or anoxia) (51). Similarly to c-Myc, the Tip110 expression level was O 2 concentration dependent (Fig.…”

Section: Discussionmentioning

confidence: 89%

“…Similar to Tip110, the expression of c-Myc protein levels in cancer cells is significantly downregulated under hypoxia and glucosedeprived conditions through UPS-mediated protein degradation (51). Suppression of c-Myc decreases necrotic cell death induced by oxygen and glucose deprivation, which might be a strategy for cancer cells to survive under conditions of limited energy resources (51).…”

Section: Discussionmentioning

confidence: 99%

Tip110 Regulates the Cross Talk between p53 and Hypoxia-Inducible Factor 1α under Hypoxia and Promotes Survival of Cancer Cells

Timani

Liu

Fan

et al. 2015

Molecular and Cellular Biology

View full text Add to dashboard Cite

bHypoxia often occurs under various physiological and pathophysiological conditions, including solid tumors; it is linked to malignant transformation, metastatic progression, and treatment failure or resistance. Tip110 protein plays important roles in several known physiological and pathophysiological processes, including cancers. Thus, in the present study we investigated the regulation of Tip110 expression under hypoxia. Hypoxia led to Tip110 protein degradation through the ubiquitin-proteasome system. Under hypoxia, Tip110 stabilized p53, which in return destabilized Tip110. In addition, Tip110 regulated hypoxia-inducible factor 1␣ (HIF-1␣), likely through enhancement of its protein stability. Furthermore, Tip110 upregulated p300, a known coactivator for both p53 and HIF-1␣. Expression of a p53(22/23) mutant deficient in p300 binding accelerated Tip110 degradation under hypoxia. Tip110 knockdown resulted in the inhibition of cell proliferation and cell death in the presence of p53. Finally, significantly less Tip110, p53, and HIF-1␣ was detected in the hypoxic region of bone metastasis tumors in a mouse model of human melanoma cells. Taken together, these results suggest Tip110 is an important mediator in the cross talk between p53 and HIF-1␣ in response to hypoxic stress. Hypoxia is the common characteristic of many solid tumors. The adaptation of cells to hypoxia is mediated by hypoxiainducible factor (HIF), a transcription factor, at the molecular level (1). Under normal oxygen conditions (normoxia), HIF-1␣ is hydroxylated, which promotes its binding to the ubiquitin ligase von Hippel-Lindau protein (pVHL), thereby targeting it for ubiquitin-proteasome system (UPS)-mediated degradation. However, under hypoxic conditions, HIF-1␣ becomes less hydroxylated, leading to its rapid accumulation and subsequent activation of hundreds of genes involved in cell survival, as well as genes involved in apoptosis (2). This opposing function of HIF in determining different cell fates is dependent on the physiopathological context and differential binding to other key partners, such as tumor suppressor protein p53.Similarly to HIF-1␣, p53 stability is also regulated by the hypoxic condition. p53 plays a crucial role in response to DNA damage, aberrant cell control, apoptosis, and senescence (3, 4). p53 function is constitutively regulated in different types of tumors under hypoxia by different mechanisms, such as p53 mutation, expression of inhibitors, or unknown host regulatory elements leading to induction of resistance to p53-mediated apoptosis. In normal cells, p53 protein expression is maintained at a low, often undetectable level due to ubiquitin-mediated proteasome degradation (5). Upon exposure to stress, such as oncogenic activation and certain hypoxic situations, p53 becomes stabilized. Consequently, p53 activates genes involved in cell cycle regulation and genes involved in apoptotic events (4).HIV-1 Tat-interacting protein 110 (Tip110), also known as "squamous cell carcinoma antigen recognized by T cells 3" (SA...

show abstract

Downregulation of c-MYC Protein Levels Contributes to Cancer Cell Survival under Dual Deficiency of Oxygen and Glucose

Cited by 89 publications

References 48 publications

Mammalian MYC Proteins and Cancer

Mammalian MYC Proteins and Cancer

Overexpression of MYC binding protein promotes invasion and migration in gastric cancer

Tip110 Regulates the Cross Talk between p53 and Hypoxia-Inducible Factor 1α under Hypoxia and Promotes Survival of Cancer Cells

Contact Info

Product

Resources

About