Prohibitin 1 Acts As a Negative Regulator of Wingless/Integrated‐Beta‐Catenin Signaling in Murine Liver and Human Liver Cancer Cells

Mavila, Nirmala; Tang, Yuanyuan; Berlind, Joshua; Ramani, Komal; Wang, Jiaohong; Mato, José M.; Lu, Shelly C.

doi:10.1002/hep4.1257

Cited by 15 publications

(18 citation statements)

References 45 publications

(83 reference statements)

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“…Accordingly inhibitors of PI3K signaling have been suggested as potential therapeutic agents in NSCLC . Some studies have found that PI3K‐AKT‐mTOR may negatively regulate the classic WNT signaling pathway through the downstream effector GSK3β . The relationship between circ‐IGF1R and key factors such as GSK3β may also be worth exploring in the future.…”

Section: Discussionmentioning

confidence: 99%

“…46,47 Some studies have found that PI3K-AKT-mTOR may negatively regulate the classic WNT signaling pathway through the downstream effector GSK3β. 48,49 The relationship between circ-IGF1R and key factors such as GSK3β may also be worth exploring in the future. It was revealed that circ-IGF1R not only affects HCC through PI3K-AKT-mTOR, but also may promote the growth and metastasis of lung cancer through PI3K-AKT-mTOR.…”

Section: Discussionmentioning

confidence: 99%

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Circ‐IGF1Rinhibits cell invasion and migration in non‐small cell lung cancer

Xiang

Chen

et al. 2020

Thoracic Cancer

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Background Circular RNA (circRNA) is a novel molecular marker and target candidate that is closely associated with tumor invasion and migration. The mechanism of action of hsa_circ_0005035 (circ‐IGF1R) in non‐small cell lung cancer remains unclear. In this study, we aimed to study the mechanism of action of circ‐IGF1R in lung cancer. Methods We screened circ‐IGF1R, one of the most notable differential expressions, from the Gene Expression Omnibus database, GSE104854, for further research. The expression level of circ‐IGF1R was examined using quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) in five different lung cancer cell lines and 50 pairs of lung cancer and adjacent tissues. Wound‐healing and Transwell assays were used for verifying the biological function of circ‐IGF1R. The effect of overexpressing circ‐IGF1R on the transcriptome of whole lung cancer cells was explored in lung cancer cell lines using RNA‐seq. Results The expression level of circ‐IGF1R was notably lower in lung cancer tissues and lung cancer cell lines than in the adjacent normal tissues and cells (P < 0.0001). In addition, the expression level of circ‐IGF1R was associated with larger tumors (T2/T3/T4) and lymph node metastasis (N1/ N2/N3) (P < 0.05). The overexpression of circ‐IGF1R significantly inhibited the invasion and migration of the lung cancer cells. The potential network of circ‐IGF1R–miR‐1270–VANGL2 was preliminarily determined, and the expression patterns of miR‐1270 and VANGL2 were verified in lung cancer cell lines. Conclusion Circ‐IGF1R may inhibit lung cancer invasion and migration through a potential network of circ‐IGF1R–miR‐1270–VANGL2.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Circ‐IGF1Rinhibits cell invasion and migration in non‐small cell lung cancer

Xiang

Chen

et al. 2020

Thoracic Cancer

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“…7 PHB1 also acts as a negative regulator of the Wingless-related integration site (WNT)/β-catenin signaling in the liver, in part through E2F1. 8 Finally, we recently showed that reduced PHB1 expression induced interleukin-8 ( IL-8 ) transcription by activating nuclear factor-kappa B (NF-κB) and activator protein 1 (AP-1), which resulted in enhanced IL-8 expression and release to promote tumorigenesis. 9 PHB1 was unable to bind to the IL-8 promoter by itself but it was able to bind in the presence of c-JUN, a finding that suggests the possibility of PHB1 acting as a co-repressor of the AP-1 site.…”

Section: Nuclear Phb1mentioning

confidence: 99%

“…1 In the liver, PHB1 acts mainly as a tumor suppressor and its deficiency results in liver injury and cancer. 4–9 This review examines the role of PHB1 in liver pathology focusing on the how its subcellular localizations, PTMs, and interactome may regulate its different functions.…”

Section: Introductionmentioning

confidence: 99%

Prohibitin 1 in liver injury and cancer

Barbier-Torres

2020

Exp Biol Med (Maywood)

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Prohibitin 1 is an evolutionary conserved and ubiquitously expressed protein that exerts different biological functions depending on its subcellular localization. The role of prohibitin 1 in liver cancer is controversial as it can be pro- or anti-tumorigenic. However, most of the studies to date have described prohibitin 1 primarily as a tumor suppressor in the liver. Its deficiency sensitizes the liver to cholestatic liver injury, non-alcoholic fatty liver disease, inflammatory insults, and cancer. Liver-specific Phb1-knockout mice spontaneously develop hepatocellular carcinoma, Phb1 heterozygotes are more susceptible to develop cholangiocarcinoma, and the majority of human hepatocellular carcinomas and cholangiocarcinomas have reduced prohibitin 1 expression. Consistent with a tumor suppressive role in the liver, prohibitin 1 negatively regulates proliferation in hepatocytes and human hepatocellular carcinoma and cholangiocarcinoma cell lines, and multiple oncogenic signaling pathways are activated when prohibitin 1 is deficient. Although best known as a mitochondrial chaperone, prohibitin 1 can protect the liver by mitochondrial-independent mechanisms. This review summarizes what’s known about prohibitin 1’s role in liver pathology, with the focus on hepatoprotection and carcinogenesis. Impact statement This review summarizes the last decades of research on PHB1 in liver pathobiology. PHB1 is a key player for liver health as it is hepatoprotective and tumor suppressive. We highlight the importance of PHB1’s subcellular localization, post-translational modifications, and interacting proteins as major determinants of PHB1 cytoprotective function and anti-tumor activity in the liver.

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“…Reduced PHB1 expression has also been shown to induce IL-8 transcription by activating NF-κB and AP-1, resulting in enhanced IL-8 expression and release to promote tumorigenesis[99]. Finally, PHB1 also acts as a negative regulator of WNT signaling, and its downregulation causes the induction of multiple WNT ligands and downstream activation of canonical WNT ‐β‐-catenin signaling in murine liver and human HCC cells, in part through E2F[100].…”

Section: Consequences Of Mat Genes Dysregulation In the Development Omentioning

confidence: 99%

Methionine adenosyltransferases in liver cancer

Murray¹,

Barbier-Torres²,

Fan³

et al. 2019

WJG

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Methionine adenosyltransferases (MATs) are essential enzymes for life as they produce S-adenosylmethionine (SAMe), the biological methyl donor required for a plethora of reactions within the cell. Mammalian systems express two genes, MAT1A and MAT2A , which encode for MATα1 and MATα2, the catalytic subunits of the MAT isoenzymes, respectively. A third gene MAT2B , encodes a regulatory subunit known as MATβ which controls the activity of MATα2. MAT1A , which is mainly expressed in hepatocytes, maintains the differentiated state of these cells, whilst MAT2A and MAT2B are expressed in extrahepatic tissues as well as non-parenchymal cells of the liver ( e.g ., hepatic stellate and Kupffer cells). The biosynthesis of SAMe is impaired in patients with chronic liver disease and liver cancer due to decreased expression and inactivation of MATα1. A switch from MAT1A to MAT2A/MAT2B occurs in multiple liver diseases and during liver growth and dedifferentiation, but this change in the expression pattern of MATs results in reduced hepatic SAMe level. Decades of study have utilized the Mat1a -knockout (KO) mouse that spontaneously develops non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) to elucidate a variety of mechanisms by which MAT proteins dysregulation contributes to liver carcinogenesis. An increasing volume of work indicates that MATs have SAMe-independent functions, distinct interactomes and multiple subcellular localizations. Here we aim to provide an overview of MAT biology including genes, isoenzymes and their regulation to provide the context for understanding consequences of their dysregulation. We will highlight recent breakthroughs in the field and underscore the importance of MAT’s in liver tumorigenesis as well as their potential as targets for cancer therapy.

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Prohibitin 1 Acts As a Negative Regulator of Wingless/Integrated‐Beta‐Catenin Signaling in Murine Liver and Human Liver Cancer Cells

Cited by 15 publications

References 45 publications

Circ‐IGF1Rinhibits cell invasion and migration in non‐small cell lung cancer

Circ‐IGF1Rinhibits cell invasion and migration in non‐small cell lung cancer

Prohibitin 1 in liver injury and cancer

Methionine adenosyltransferases in liver cancer

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