ATF3 inhibits the tumorigenesis and progression of hepatocellular carcinoma cells via upregulation of CYR61 expression

Chen, Cong; Ge, Chao; Liu, Zheng; Li, Liangyu; Zhao, Fangyu; Tian, Hua; Chen, Taoyang; Li, Hong; Yao, Ming; Li, Jinjun

doi:10.1186/s13046-018-0919-8

Cited by 57 publications

(54 citation statements)

References 44 publications

(46 reference statements)

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“…11 In contrast Chen et al reported that ATF3 inhibited hepatocellular carcinoma carcinogenesis. 12 However, the detailed molecular mechanisms of ATF3 in breast cancer tumorigenesis have not been characterized. In this study, we quantified the expression of ATF3 in breast cancer and investigated the effects of DNA methylation on ATF3 expression.…”

Section: Introductionmentioning

confidence: 99%

<p>ATF3 Demethylation Promotes the Transcription of ARL4C, Which Acts as a Tumor Suppressor in Human Breast Cancer</p>

Sun

Jiang

2020

OTT

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Introduction: Breast cancer is a common malignancy in females worldwide. In this study, we investigated the role of activating transcription factor 3 (ATF3) and ADP-ribosylation factor like-4 (ARL4) in human breast cancer, and the associated mechanisms. Materials and Methods: We measured ATF3 and ATL4C expressions in 15 paired breast cancer tissues using qRT-PCR, Western blotting and IHC. Cell growth, migration and invasion were tested in ATF3 or ARL4C overexpression breast cancer cells. TCGA database analysis was done to identify the correlation between ATF3 and ARL4C. We evaluated the binding of ATF3 to ARL4C promoter sequences and the effect of hypermethylation and demethylation of ATF3. A meta-analysis was done to investigate the relationship between the expression of ATF3 and/or ARL4C and the poor prognoses. Results: Our results showed that ATF3 and ARL4C were decreased in breast cancer specimens at both mRNA and protein levels. Restoration of ATF3 or ARL4C reduced breast cancer tumorigenesis, evidenced by decreased cell growth, migration and invasion. The expression of ATF3 was positively correlated with ARL4C in breast cancer specimens, and ATF3 was shown to bind to the ARL4C promoter sequences. Furthermore, the expression of ATF3 was negatively regulated by hypermethylation, and demethylation of ATF3 stimulated ATF3 expression, which further promoted ARL4C transcription. Finally, a meta-analysis showed that patients with breast cancer with lower expression levels of ATF3 and/or ARL4C had worse prognoses. Conclusion: Our results suggest that the ATF3/ARL4C axis may be a prospective biomarker for diagnosis and determination of prognosis, and a potential target for breast cancer treatment.

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Section: Introductionmentioning

confidence: 99%

<p>ATF3 Demethylation Promotes the Transcription of ARL4C, Which Acts as a Tumor Suppressor in Human Breast Cancer</p>

Sun

Jiang

2020

OTT

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“…On the other hand, several studies have reported oncosuppressive roles of ATF3. Its overexpression in liver cancer and hepatocellular carcinoma cells reduced proliferation and motility while apoptosis was increased [ 51 , 52 ]. Other reports showed ATF3 as inhibitor of invasion and migration both in colorectal cancer and ovarian cancer cells [ 53 , 54 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

Time-Resolved Profiling Reveals ATF3 as a Novel Mediator of Endocrine Resistance in Breast Cancer

Borgoni

Sofyalı

Soleimani

et al. 2020

Cancers

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Breast cancer is one of the leading causes of death for women worldwide. Patients whose tumors express Estrogen Receptor α account for around 70% of cases and are mostly treated with targeted endocrine therapy. However, depending on the degree of severity of the disease at diagnosis, 10 to 40% of these tumors eventually relapse due to resistance development. Even though recent novel approaches as the combination with CDK4/6 inhibitors increased the overall survival of relapsing patients, this remains relatively short and there is a urgent need to find alternative targetable pathways. In this study we profiled the early phases of the resistance development process to uncover drivers of this phenomenon. Time-resolved analysis revealed that ATF3, a member of the ATF/CREB family of transcription factors, acts as a novel regulator of the response to therapy via rewiring of central signaling processes towards the adaptation to endocrine treatment. ATF3 was found to be essential in controlling crucial processes such as proliferation, cell cycle, and apoptosis during the early response to treatment through the regulation of MAPK/AKT signaling pathways. Its essential role was confirmed in vivo in a mouse model, and elevated expression of ATF3 was verified in patient datasets, adding clinical relevance to our findings. This study proposes ATF3 as a novel mediator of endocrine resistance development in breast cancer and elucidates its role in the regulation of downstream pathways activities.

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“…On the other hand, several studies have reported 443 oncosuppressive roles of ATF3. Its overexpression in liver cancer and hepatocellular carcinoma 444 cells reduced proliferation and motility while apoptosis was increased 38,39 . Other reports 445 showed ATF3 as inhibitor of invasion and migration both in colorectal cancer and ovarian 446 cancer cells [40][41][42] .…”

Section: Reverse Phase Protein Array 358mentioning

confidence: 99%

Time-resolved profiling reveals ATF3 as a novel mediator of endocrine resistance in breast cancer

Borgoni

Sofyalı

Soleimani

et al. 2020

Preprint

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39Breast cancer is one of the leading causes of death for women worldwide. Patients whose 40 tumors express Estrogen Receptor α (ERα) account for around 70% of cases and are mostly 41 treated with targeted endocrine therapy. However, 40% of these tumors eventually relapse due 42 to resistance development and further treatment of these patients is highly ineffective. In this 43 study we profiled the early phases of the resistance development process to uncover drivers of 44 this phenomenon. Time-resolved analysis revealed that ATF3, a member of the ATF/CREB 45 family of transcription factors, acts as a novel regulator of the response to therapy via rewiring 46 of central signaling processes towards the adaptation to endocrine treatment. ATF3 was found 47 to be essential in controlling crucial processes such as proliferation, cell cycle and apoptosis 48 during the early response to treatment through the regulation of MAPK/AKT signaling 49 pathways. Its essential role was confirmed in vivo in a mouse model and elevated expression of 50 ATF3 was verified in patient datasets, adding clinical relevance to our findings. This study 51 proposes ATF3 as a novel mediator of endocrine resistance development in breast cancer and 52 elucidates its role in the regulation of downstream pathways activities. 53 54 55 56 57 Breast cancer/ endocrine therapy / drug-resistance / ATF3 / RPPA 58 4 59 60 Breast cancer is the most diagnosed type of cancer among women and the second-leading 61 cause of death after lung cancer 1 . It is a highly heterogeneous disease and the clinical sub-62 typing is based on the expression of estrogen receptor (ER), progesterone receptor (PR), HER2 63 receptor (HER2) and Ki-67 2 . Based on these markers the tumors are divided into Luminal A, 64 Luminal B, HER2 enriched and Triple negative 3 . Luminal tumors are the most abundant subtype, 65accounting for around 70% of all breast cancers, for which endocrine therapy is the standard 66 treatment 4,5 . Endocrine therapy consists of different drugs that act on ER activation, including 67 selective ER modulators (SERMs) and downregulators (SERDs), like tamoxifen and fulvestrant, 68 respectively, and aromatase inhibitors (AIs), that block the enzymes involved in the synthesis of 69 estrogens 6 . 70Despite the clear benefit of endocrine therapy for patients with ER+ breast cancer, resistance to 71 treatment is a critical clinical issue that affects approximately 10-15% of patients in the first 5 72 years 7 and up to 30-40% within 15 years from the start of the treatment 8,9 . After the failure of 73 first line endocrine therapy, recurrent ER+ breast cancer can be treated with alternative 74 strategies to target growth and survival pathways. Common strategies employ fulvestrant to 75 block and degrade the ER both in monotherapy or in combination with other approved drugs 76 for advanced breast cancer, such as CDK4/6, mTOR and PI3K inhibitors 10 . 77

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ATF3 inhibits the tumorigenesis and progression of hepatocellular carcinoma cells via upregulation of CYR61 expression

Cited by 57 publications

References 44 publications

<p>ATF3 Demethylation Promotes the Transcription of ARL4C, Which Acts as a Tumor Suppressor in Human Breast Cancer</p>

<p>ATF3 Demethylation Promotes the Transcription of ARL4C, Which Acts as a Tumor Suppressor in Human Breast Cancer</p>

Time-Resolved Profiling Reveals ATF3 as a Novel Mediator of Endocrine Resistance in Breast Cancer

Time-resolved profiling reveals ATF3 as a novel mediator of endocrine resistance in breast cancer

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