ACTL6A interacts with p53 in acute promyelocytic leukemia cell lines to affect differentiation via the Sox2/Notch1 signaling pathway

Zhong, Pengqiang; Liu, Zhong; Yao, Juanjuan; Liu, Dongdong; Yuan, Zhen; Liu, Junmei; Chen, Min; Yao, Shifei; Zhao, Yi; Liu, Lu; Li, Lianwen; Liu, Beizhong

doi:10.1016/j.cellsig.2018.11.009

Cited by 16 publications

(14 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies have revealed that ACTL6A is oncogenic in human cancer [12–13]. Some studies have illustrated that overexpressed ACTL6A promotes epithelial-mesenchymal transition (EMT) and invasion in multiple cancers, such as osteosarcoma, hepatocellular carcinoma, and glioma [14–16]. Thus, ACTL6A could function as a new prognostic indicator.…”

Section: Discussionmentioning

confidence: 99%

The genetic alteration spectrum of the SWI/SNF complex: The oncogenic roles of BRD9 and ACTL6A

Sima

Peng

et al. 2019

PLoS ONE

View full text Add to dashboard Cite

SWItch/Sucrose NonFermentable (SWI/SNF) is a set of multi-subunits chromatin remodeling complexes, playing important roles in a variety of biological processes. Loss-of-function mutations in the genes encoding SWI/SNF subunits have been reported in more than 20% of human cancers. Thus, it was widely considered as a tumor suppressor in the past decade. However, recent studies reported that some genes encoding subunits of SWI/SNF complexes were amplified and play oncogenic roles in human cancers. In present study, we summarized the genetic alteration spectrum of SWI/SNF complexes, and firstly systematically estimated both the copy number variations and point mutations of all 30 genes encoding the subunits in this complex. Additionally, the bioinformatics analyses were performed for two significantly amplified genes, ACTL6A and BRD9, to investigate their oncogenic roles in human cancers. Our findings may lay a foundation for the discovery of potential treatment targets in SWI/SNF complexes of cancers.

show abstract

Section: Discussionmentioning

confidence: 99%

The genetic alteration spectrum of the SWI/SNF complex: The oncogenic roles of BRD9 and ACTL6A

Sima

Peng

et al. 2019

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Mechanistically, ACTL6A overexpression promoted migration and invasion and induced EMT in vitro [283,284] and promoted tumor growth and metastasis in a mouse liver cancer xenograft model [283]. Further studies demonstrated that ACTL6A targets SOX2 expression, which activates Notch1 signaling, leading to EMT [282,283].…”

Section: Actl6amentioning

confidence: 97%

“…Amplifications of ACTL6A are associated with PDAC (Table 1); however, mechanistic studies in PDAC are missing. Several studies demonstrated that ACTL6A is amplified and upregulated in different cancers [137,[281][282][283][284][285]. ACTL6A has a protumorigenic function and its expression level correlated with worse clinicopathological features in liver cancer and in colon cancer [283,284].…”

Section: Actl6amentioning

confidence: 99%

“…Moreover, ACTL6A is associated with stem cell maintenance [107,281,282,286], including activation of the Hippo-YAP pathway [281], Nanog binding to pluripotency genes, and repression of differentiation genes [286], which might explain its role in cancer. As ACTL6A promotes a stem-cell-like state, it is not surprising that its levels are increased in cancer.…”

Section: Actl6amentioning

confidence: 99%

See 1 more Smart Citation

The Emerging Roles of ATP-Dependent Chromatin Remodeling Complexes in Pancreatic Cancer

Hasan

Ahuja

2019

Cancers

View full text Add to dashboard Cite

Pancreatic cancer is an aggressive cancer with low survival rates. Genetic and epigenetic dysregulation has been associated with the initiation and progression of pancreatic tumors. Multiple studies have pointed to the involvement of aberrant chromatin modifications in driving tumor behavior. ATP-dependent chromatin remodeling complexes regulate chromatin structure and have critical roles in stem cell maintenance, development, and cancer. Frequent mutations and chromosomal aberrations in the genes associated with subunits of the ATP-dependent chromatin remodeling complexes have been detected in different cancer types. In this review, we summarize the current literature on the genomic alterations and mechanistic studies of the ATP-dependent chromatin remodeling complexes in pancreatic cancer. Our review is focused on the four main subfamilies: SWItch/sucrose non-fermentable (SWI/SNF), imitation SWI (ISWI), chromodomain-helicase DNA-binding protein (CHD), and INOsitol-requiring mutant 80 (INO80). Finally, we discuss potential novel treatment options that use small molecules to target these complexes.

show abstract

“…HL-60 cells is a widely used model system for studying the molecular events of AML, which lack the t(15;17) translocation characteristic of most cases of APL 13,22,23 . However, HL-60 can respond to ATRA 22 , which is widely used as a cell line in the APL studies [24][25][26][27] . In our previous study 28 , consistent to previous reports 15,[19][20][21] , we also found celastrol caused apoptosis in HL-60 cells, indicating the key role of apoptosis in the effect of celastol in the treatment of acute leukemia.…”

mentioning

confidence: 99%

Metabolomics Reveals that Cysteine Metabolism Plays a Role in Celastrol-Induced Mitochondrial Apoptosis in HL-60 and NB-4 Cells

Chen

Yang

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Recently, celastrol has shown great potential for inducing apoptosis in acute myeloid leukemia cells, especially acute promyelocytic leukaemia cells. However, the mechanism is poorly understood. Metabolomics provides an overall understanding of metabolic mechanisms to illustrate celastrol's mechanism of action. We treated both nude mice bearing HL-60 cell xenografts in vivo and HL-60 cells as well as NB-4 cells in vitro with celastrol. Ultra-performance liquid chromatography coupled with mass spectrometry was used for metabolomics analysis of HL-60 cells in vivo and for targeted L-cysteine analysis in HL-60 and NB-4 cells in vitro. Flow cytometric analysis was performed to assess mitochondrial membrane potential, reactive oxygen species and apoptosis. Western blotting was conducted to detect the p53, Bax, cleaved caspase 9 and cleaved caspase 3 proteins. Celastrol inhibited tumour growth, induced apoptosis, and upregulated pro-apoptotic proteins in the xenograft tumour mouse model. Metabolomics showed that cysteine metabolism was the key metabolic alteration after celastrol treatment in HL-60 cells in vivo. Celastrol decreased L-cysteine in HL-60 cells. Acetylcysteine supplementation reversed reactive oxygen species accumulation and apoptosis induced by celastrol and reversed the dramatic decrease in the mitochondrial membrane potential and upregulation of pro-apoptotic proteins in HL-60 cells. In NB-4 cells, celastrol decreased L-cysteine, and acetylcysteine reversed celastrol-induced reactive oxygen species accumulation and apoptosis. We are the first to identify the involvement of a cysteine metabolism/reactive oxygen species/p53/Bax/caspase 9/ caspase 3 pathway in celastrol-triggered mitochondrial apoptosis in HL-60 and NB-4 cells, providing a novel underlying mechanism through which celastrol could be used to treat acute myeloid leukaemia, especially acute promyelocytic leukaemia.Acute leukemia is the most common malignant hematological malignancy, of which acute myeloid leukemia (AML) accounts for over 80% of all acute leukemias in individuals aged >18 years 1 . Chemotherapy is the main treatment of AML. There are still problems such as drug resistance and relapse of leukemia after drug withdrawal, which seriously affect the quality of life and long-term survival of patients. Therefore, it is of great significance to find effective new antineoplastic drugs and explore new therapeutic schemes.Acute promyelocytic leukaemia (APL), a unique subtype of acute myeloid leukaemia (AML), is a devastating disease characterized by neoplastic proliferation of cells in the bone marrow that have a promyelocytic phenotype and fail to terminally differentiate 2 . Unlike other forms of AML, APL can cause diffuse intravascular coagulopathy

show abstract

ACTL6A interacts with p53 in acute promyelocytic leukemia cell lines to affect differentiation via the Sox2/Notch1 signaling pathway

Cited by 16 publications

References 33 publications

The genetic alteration spectrum of the SWI/SNF complex: The oncogenic roles of BRD9 and ACTL6A

The genetic alteration spectrum of the SWI/SNF complex: The oncogenic roles of BRD9 and ACTL6A

The Emerging Roles of ATP-Dependent Chromatin Remodeling Complexes in Pancreatic Cancer

Metabolomics Reveals that Cysteine Metabolism Plays a Role in Celastrol-Induced Mitochondrial Apoptosis in HL-60 and NB-4 Cells

Contact Info

Product

Resources

About