Synergistic Activation of the Tumor Suppressor, HLJ1, by the Transcription Factors YY1 and Activator Protein 1

Wang, Chi Chung; Tsai, Meng Feng; Dai, Ting Hao; Hong, Tse-Ming; Chan, Wing Kai; Chen, Jeremy J.W.; Yang, Pan‐Chyr

doi:10.1158/0008-5472.can-07-0504

Cited by 54 publications

(53 citation statements)

References 38 publications

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“…Because YY1 positively regulates expression of several oncogenes, that is, E6 and E7, c-Myc, c-Fos and ErbB2 (Riggs et al, 1993;Lee et al, 1995a, b), and negatively regulates p53 stability (Gronroos et al, 2004;Sui et al, 2004), it is believed that YY1 acts as an oncogene (Gordon et al, 2006;Castellano et al, 2009). On the other hand, YY1 also inhibits cancer cell growth through binding and inhibiting c-Myc function (Austen et al, 1998), and positively regulates expression of a number of genes with tumor suppressor function such as HLJ1, p73 and p53 (Furlong et al, 1996;Wang et al, 2005Wang et al, , 2007Wu et al, 2007a). These data suggest that YY1 can act as both a tumor suppressor and an oncogene, depending on tissue context and distribution of its downstream genes.…”

Section: Yy1 Activates Brca1 Transcription M-h Lee Et Almentioning

confidence: 99%

“…On the other hand, YY1 serves as a positive regulator for a number of genes with tumor suppressor function, such as DnaJ-like heat shock protein 40, HLJ1 (Wang et al, 2005(Wang et al, , 2007, p73 (Wu et al, 2007a) and p53 (Furlong et al, 1996) through various mechanisms. YY1 also acts as a negative regulator of cell growth through binding and inhibiting c-Myc function (Austen et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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Yin Yang 1 positively regulates BRCA1 and inhibits mammary cancer formation

Lee

Lahusen

et al. 2011

Oncogene

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Expression of the breast cancer-associated gene 1 (BRCA1) in sporadic breast cancers is usually reduced, yet the underlying mechanisms remains elusive. To identify factors that are responsible for reduced BRCA1 expression, we screened 92 known transcription factors for their ability to regulate expression of BRCA1. Among several potential regulators, the Gli-Krueppel-related transcription factor Yin Yang 1 (YY1) showed the most dramatic transactivation of the BRCA1 promoter. YY1 binds to the promoter of BRCA1, and its overexpression resulted in increased expression of BRCA1 and a number of BRCA1 downstream genes. We further showed that overexpression of YY1 in cancer cells inhibited cell proliferation, foci formation and tumor growth in nude mice. To assess the clinical relevance between YY1 and BRCA1, we studied expression of YY1 and BRCA1 from human breast cancer samples and tissue arrays, and detected a significant positive correlation between the level of YY1 and BRCA1 expression in these cancers. Taken together, these findings suggest that YY1 is a key regulator of BRCA1 expression and may be causally linked to the molecular etiology of human breast cancer.

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Section: Yy1 Activates Brca1 Transcription M-h Lee Et Almentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Yin Yang 1 positively regulates BRCA1 and inhibits mammary cancer formation

Lee

Lahusen

et al. 2011

Oncogene

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“…The role of HLJ1, a member of the human heat shock protein 40 (HSP40) family, in lung cancer development and progression has been extensively investigated [19][20][21] . HLJ1 has been characterised as a tumour suppressor, and research studies have identified the protein's promising dual anticancer effects in NSCLC, inhibiting both tumour growth and metastasis [19,22,23] .…”

Section: Introductionmentioning

confidence: 99%

Tumour suppressor HLJ1: A potential diagnostic, preventive and therapeutic target in non-small cell lung cancer

Tsai¹

2014

WJCO

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Lung cancer is the leading cause of cancer-related mortality throughout the world. Non-small cell lung cancer (NSCLC) accounts for 85% of all diagnosed lung cancers. Despite considerable progress in the diagnosis and treatment of the disease, the overall 5-year survival rate of NSCLC patients remains lower than 15%. The most common causes of death in lung cancer patients are treatment failure and metastasis. Therefore, developing novel strategies that target both tumour growth and metastasis is an important and urgent mission for the next generation of anticancer therapy research. Heat shock proteins (HSPs), which are involved in the fundamental defence mechanism for maintaining cellular viability, are markedly activated during environmental or pathogenic stress. HSPs facilitate rapid cell division, metastasis, and the evasion of apoptosis in cancer development. These proteins are essential players in the development of cancer and are prime therapeutic targets. In this review, we focus on the current understanding of the molecular mechanisms responsible for HLJ1's role in lung cancer carcinogenesis and progression. HLJ1, a member of the human HSP 40 family, has been characterised as a tumour suppressor. Research studies have also reported that HLJ1 shows promising dual anticancer effects, inhibiting both tumour growth and metastasis in NSCLC. The accumulated evidence suggests that HLJ1 is a potential biomarker and treatment target for NSCLC.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Non-small cell lung cancer; Metastasis; HLJ1; Anticancer; Biomarker Core tip: HLJ1, a member of the human heat shock proteins 40 family, has been characterised as a tumour suppressor. Research studies have reported that HLJ1 shows promising dual anticancer effects, inhibiting both tumour growth and metastasis in non-small cell lung cancer (NSCLC). The accumulated evidence suggests that HLJ1 is a potential biomarker and treatment target for NSCLC. We propose a hypothetical model for the roles of HLJ1 stimulator in suppressing lung cancer tumourigenesis. Investigating the integrated and coordinated molecular mechanisms of HLJ1 may shed new light on the treatment of lung cancer. The development of drug targeting HLJ1 may be an effective approach for lung cancer therapy.Tsai MF, Wang CC, Chen JJW. Tumour suppressor HLJ1: A potential diagnostic, preventive and therapeutic target in nonsmall cell lung cancer.

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“…In this context, HLJ1 (DNAJB4) belongs to the DNAJ (HSP40) family of HSPs and is regarded as a tumor suppressor gene in lung, colon, and gastric cancers (Liu et al, 2014;Simões-correia et al, 2014;Tsai et al, 2006;Wang et al, 2005). HLJ1 has also been suggested as a potential biomarker and therapeutic target in lung cancer (Chen et al, 2008;Lai et al, 2013;Tsai et al, 2006;Wang et al, 2007). Moreover, in vitro studies showed that induction of HLJ1 inhibits cancer cell invasion in hepatocellular carcinoma cells (Wang et al, 2007).…”

mentioning

confidence: 99%

“…HLJ1 has also been suggested as a potential biomarker and therapeutic target in lung cancer (Chen et al, 2008;Lai et al, 2013;Tsai et al, 2006;Wang et al, 2007). Moreover, in vitro studies showed that induction of HLJ1 inhibits cancer cell invasion in hepatocellular carcinoma cells (Wang et al, 2007). Importantly, the role of HLJ1 remains unclear in breast cancer despite the growing importance of this molecular target in abovementioned cancer types.…”

mentioning

confidence: 99%

HLJ1 (DNAJB4) Gene Is a Novel Biomarker Candidate in Breast Cancer

Acun

Doberstein

Habermann

et al. 2017

OMICS: A Journal of Integrative Biology

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Breast cancer is the most common cancer type and cause of cancer-related mortality among women worldwide. New biomarker discovery is crucial for diagnostic innovation and personalized medicine in breast cancer. Heat shock proteins (HSPs) have been increasingly reported as biomarkers and potential drug targets for cancers. HLJ1 (DNAJB4) belongs to the DNAJ (HSP40) family of HSPs and is regarded as a tumor suppressor gene in lung, colon, and gastric cancers. However, the role of the HLJ1 gene in breast cancer is currently unknown. We evaluated the role of the HLJ1 gene in breast cancer progression by analyzing its in vitro and in vivo expression and its genetic/epigenetic alterations. HLJ1 expression was found to be reduced or lost in breast cancer cell lines (SK-BR-3, MDA-MB-231, ZR-75-1) compared with the nontumorigenic mammary epithelial cell line (MCF 10A). In a clinical context for breast cancer progression, the HLJ1 expression was significantly less frequent in invasive breast carcinoma samples (n = 230) compared with normal breast tissue (n = 100), benign neoplasia (n = 53), and ductal carcinoma in situ (n = 21). In methylation analyses by the combined bisulfite restriction analysis assay, the CpG island located in the 5¢-flanking region of the HLJ1 gene was found to be methylated in breast cancer cell lines. HLJ1 expression was restored in the ZR-75-1 cell line by DNA demethylating agent 5-Aza-2¢-deoxycytidine (5-AzadC) and histone deacetylase inhibitor trichostatin A. These new observations support the idea that HLJ1 is a tumor suppressor candidate and potential biomarker for breast cancer. Epigenomic mechanisms such as CpG methylation and histone deacetylation might contribute to downregulation of HLJ1 expression. We call for future functional, epigenomic, and clinical studies to ascertain the contribution of HLJ1 to breast cancer pathogenesis and, importantly, evaluate its potential for biomarker development in support of personalized medicine diagnostic innovation in clinical oncology.

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Synergistic Activation of the Tumor Suppressor, HLJ1, by the Transcription Factors YY1 and Activator Protein 1

Cited by 54 publications

References 38 publications

Yin Yang 1 positively regulates BRCA1 and inhibits mammary cancer formation

Yin Yang 1 positively regulates BRCA1 and inhibits mammary cancer formation

Tumour suppressor HLJ1: A potential diagnostic, preventive and therapeutic target in non-small cell lung cancer

HLJ1 (DNAJB4) Gene Is a Novel Biomarker Candidate in Breast Cancer

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