FHL2 exhibits anti-proliferative and anti-apoptotic activities in liver cancer cells

Ng, Chor Fung; Ng, Patrick Kwok Shing; Lui, Vivian Wai Yan; Li, Jialiang; Chan, Judy Yuet-Wa; Fung, Kwok Pui; Ng, Yuen Keng; Lai, Paul B.S.; Tsui, Stephen Kwok‐Wing

doi:10.1016/j.canlet.2011.02.001

Cited by 29 publications

(23 citation statements)

References 37 publications

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“…These observations indicate that FHL2 signaling might function in a context-dependent manner, and participate to the maintenance of liver homeostasis through balanced regulation of cell proliferation and apoptosis. However, overexpression of FHL2 has been shown to exhibit anti-proliferative and anti-apoptotic activities in liver cancer cell line Hep3B [30], suggesting that the impact of FHL2 overexpression on cell proliferation and death may be different for cells that are already transformed prior to FHL2 overexpression.…”

Section: Discussionmentioning

confidence: 97%

The four and a half LIM-only protein 2 regulates liver homeostasis and contributes to carcinogenesis

Nouët

Dahan

Labalette

et al. 2012

Journal of Hepatology

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Section: Discussionmentioning

confidence: 97%

The four and a half LIM-only protein 2 regulates liver homeostasis and contributes to carcinogenesis

Nouët

Dahan

Labalette

et al. 2012

Journal of Hepatology

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“…Recently, PPAR β / δ was identified as a target gene of FHL2, a tumor suppressor gene also involved in hepatocellular carcinoma [119, 120]. …”

Section: Ppars and Mitochondrial Dysfunction From Nafld To Hccmentioning

confidence: 99%

PPARs and Mitochondrial Metabolism: From NAFLD to HCC

2016

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Metabolic related diseases, such as type 2 diabetes, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD), are widespread threats which bring about a significant burden of deaths worldwide, mainly due to cardiovascular events and cancer. The pathogenesis of these diseases is extremely complex, multifactorial, and only partially understood. As the main metabolic organ, the liver is central to maintain whole body energetic homeostasis. At the cellular level, mitochondria are the metabolic hub connecting and integrating all the main biochemical, hormonal, and inflammatory signaling pathways to fulfill the energetic and biosynthetic demand of the cell. In the liver, mitochondria metabolism needs to cope with the energetic regulation of the whole body. The nuclear receptors PPARs orchestrate lipid and glucose metabolism and are involved in a variety of diseases, from metabolic disorders to cancer. In this review, focus is placed on the roles of PPARs in the regulation of liver mitochondrial metabolism in physiology and pathology, from NAFLD to HCC.

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“…FHL2 has been implicated in many forms of cancers in which its expression was found to be deregulated [5]. The function of FHL2 in cancers is particularly intriguing because FHL2 can function as an oncoprotein or as a tumor suppressor [6] in different type of cancers, including prostate cancer [7], liver cancer [8], [9], gastrointestinal cancers [10]–[12], breast cancer [13] and osteosarcoma [14]. The functional diversity of FHL2 could be contributed by its protein partners in different signaling pathways, e.g.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Regulation of the Tumor Suppressor FHL2 by p53 in Human Kidney and Liver Cells

Zhou

et al. 2014

PLoS ONE

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Four and a Half LIM protein 2 (FHL2) is a LIM domain only protein that is able to form various protein complexes and regulate gene transcription. Recent findings showed that FHL2 is a potential tumor suppressor gene that was down-regulated in hepatocellular carcinoma (HCC). Moreover, FHL2 can bind to and activate the TP53 promoter in hepatic cells. In this study, the activity of the two promoters of FHL2, 1a and 1b, were determined in the human embryonic kidney cell line HEK293 and the activation of these two promoters by p53 was investigated. Our results showed that the 1b promoter has a higher activity than the 1a promoter in HEK 293 cells but the 1a promoter is more responsive to the activation by p53 when compared with the 1b promoter. The regulation of FHL2 by p53 was further confirmed in liver cells by the overexpression of p53 in Hep3B cells and the knockdown of p53 in HepG2 cells. Combining promoter activity results of truncated mutants and predictions by bioinformatics tools, a putative p53 binding site was found in the exon 1a of FHL2 from +213 to +232. The binding between the p53 protein and the putative p53 binding site was then validated by the ChIP assay. Furthermore, the expression of FHL2 and TP53 were down-regulated in majority of HCC tumour samples (n = 41) and significantly correlated (P = 0.026). Finally, we found that the somatic mutation 747 (G→T), a hot spot mutation of the TP53 gene, is potentially associated with a higher expression of FHL2 in HCC tumour samples. Taken together, this is the first in-depth study about the transcriptional regulation of FHL2 by p53.

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FHL2 exhibits anti-proliferative and anti-apoptotic activities in liver cancer cells

Cited by 29 publications

References 37 publications

The four and a half LIM-only protein 2 regulates liver homeostasis and contributes to carcinogenesis

The four and a half LIM-only protein 2 regulates liver homeostasis and contributes to carcinogenesis

PPARs and Mitochondrial Metabolism: From NAFLD to HCC

Transcriptional Regulation of the Tumor Suppressor FHL2 by p53 in Human Kidney and Liver Cells

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