SREBP-1 Has a Prognostic Role and Contributes to Invasion and Metastasis in Human Hepatocellular Carcinoma

Li, Chao; Yang, Wei; Zhang, Junli; Zheng, Xin; Yao, Yingmin; Tu, Kangsheng; Liu, Qingguang

doi:10.3390/ijms15057124

Cited by 107 publications

(89 citation statements)

References 26 publications

(27 reference statements)

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“…Transwell assays were done in 6 well plates with Transwell inserts equipped with 8-μm pores (Nalge Nunc International Corp, Naperville, IL, USA) coated with Matrigel at 1:6 dilution (Becton Dickinson Labware, Bedford, MA, USA) as previously described [26]. …”

Section: Methodsmentioning

confidence: 99%

TPX2 Is a Prognostic Marker and Contributes to Growth and Metastasis of Human Hepatocellular Carcinoma

Huang

Guo

Kan

2014

IJMS

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Targeting protein for Xenopus kinesin-like protein 2 (TPX2), a microtubule-associated protein, impacts spindle assembly in human cells. Several studies have demonstrated that TPX2 is overexpressed in different types of human cancers and promotes tumor growth and metastasis. In this study, we found that the expression level of TPX2 was obviously higher in hepatocellular carcinoma (HCC) tissues than in matched nontumor tissues. Elevated expressions of TPX2 mRNA were observed in all HCC cell lines (HepG2, Hep3B, SMMC-7721, Bel-7402 and Huh7) as compared with that in a non-transformed hepatic cell line (LO2). Clinical analysis indicated that the positive expression of TPX2 was significantly correlated with venous infiltration, high Edmondson-Steiner grading and advanced TNM tumor stage in HCC. Furthermore, TPX2 was a novel prognostic marker for predicting 5-year overall survival (OS) and disease-free survival (DFS) of HCC patients. In vitro studies found that TPX2 knockdown significantly inhibited cell proliferation and viability in both Hep3B and HepG2 cells. Moreover, TPX2 knockdown obviously slowed down tumor growth in a nude mouse xenograft model. Otherwise, TPX2 knockdown prominently suppressed HCC cell invasion and migration. In conclusion, these results indicate that TPX2 may serve as a prognostic marker and promotes tumorigenesis and metastasis of HCC.

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Section: Methodsmentioning

confidence: 99%

TPX2 Is a Prognostic Marker and Contributes to Growth and Metastasis of Human Hepatocellular Carcinoma

Huang

Guo

Kan

2014

IJMS

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“…Recent studies have demonstrated that both lipid synthesis and uptake are significantly elevated in malignancies to support tumor growth [10–14]. SREBP-1 is highly expressed in glioblastoma (GBM) [60, 61], the most deadly brain tumor [62], and in prostate [63], endometrial [64], breast cancers [65, 66], hepatocellular carcinoma (HCC) [67], ovarian cancer [68], and pancreatic cancer (Table 1) [69]. The function of SREBP-1 has been investigated in multiple cancer cell lines including colon [70], lung [71] and pancreatic cancer cell lines [72].…”

Section: Activation Of Scap/srebps In Cancermentioning

confidence: 99%

SCAP/SREBPs are Central Players in Lipid Metabolism and Novel Metabolic Targets in Cancer Therapy

Cheng

Guo

2018

CTMC

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Lipid metabolism reprogramming emerges as a new hallmark of malignancies. Sterol regulatory element-binding proteins (SREBPs), which are central players in lipid metabolism, are endoplasmic reticulum (ER)-bound transcription factors that control the expression of genes important for lipid synthesis and uptake. Their transcriptional activation requires binding to SREBP cleavage-activating protein (SCAP) to translocate their inactive precursors from the ER to the Golgi to undergo cleavage and subsequent nucleus translocation of their NH2-terminal forms. Recent studies have revealed that SREBPs are markedly upregulated in human cancers, providing the mechanistic link between lipid metabolism alterations and malignancies. Pharmacological or genetic inhibition of SCAP or SREBPs significantly suppresses tumor growth in various cancer models, demonstrating that SCAP/SREBPs could serve as promising metabolic targets for cancer therapy. In this review, we will summarize recent progress in our understanding of the underlying molecular mechanisms regulating SCAP/SREBPs and lipid metabolism in malignancies, discuss new findings about SREBP trafficking, which requires SCAP N-glycosylation, and introduce a newly identified microRNA-29-mediated negative feedback regulation of the SCAP/SREBP pathway. Moreover, we will review recently developed inhibitors targeting the SCAP/SREBP pathway for cancer treatment.

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“…Compared with adjacent normal tissues, SREBP‐1 expression is high in HCC tissues. The positive expression of SREBP‐1 is correlated with poor survival of HCC patients (Li et al ., 2014). SREBP transcriptional activity is generally low in normal and nonproliferating cells, which typically import lipids from the extracellular environment.…”

Section: Introductionmentioning

confidence: 99%

Role of hepatoma‐derived growth factor in promoting de novo lipogenesis and tumorigenesis in hepatocellular carcinoma

et al. 2018

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Although identified as a growth factor, the mechanism by which hepatoma‐derived growth factor (HDGF) promotes cancer development remains unclear. We found that nuclear but not cytoplasmic HDGF is closely associated with prognosis of hepatocellular carcinoma (HCC). RNA‐sequencing analysis further demonstrated that the nuclear role of HDGF involved regulation of transcription of lipid metabolism genes. HDGF‐induced expression of lipogenic genes was mainly associated with activation of sterol regulatory element binding protein (SREBP) transcription factor. Coexpression of SREBP‐1 and nuclear HDGF predicts poor prognosis for HCC. In addition, by changing the first amino acid of the PWWP domain from proline to alanine, the type of PWWP domain changed from P‐ to A‐type, resulting in inability to induce SREBP‐1‐mediated gene transcription. The type of PWWP domain affects the recruitment of the C‐terminal binding protein‐1 transcriptional repressor on the promoter of the lipogenic gene. Our data indicate that HDGF acts as a coactivator of SREBP1‐mediated transcription of lipogenic genes. The PWWP domain is crucial for HDGF to promote lipogenesis. Moreover, transcriptional regulation of nuclear HDGF plays important roles in the development of HCC.

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SREBP-1 Has a Prognostic Role and Contributes to Invasion and Metastasis in Human Hepatocellular Carcinoma

Cited by 107 publications

References 26 publications

TPX2 Is a Prognostic Marker and Contributes to Growth and Metastasis of Human Hepatocellular Carcinoma

TPX2 Is a Prognostic Marker and Contributes to Growth and Metastasis of Human Hepatocellular Carcinoma

SCAP/SREBPs are Central Players in Lipid Metabolism and Novel Metabolic Targets in Cancer Therapy

Role of hepatoma‐derived growth factor in promoting de novo lipogenesis and tumorigenesis in hepatocellular carcinoma

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