HSP4 triggers epithelial‐mesenchymal transition and promotes motility capacities of hepatocellular carcinoma cells via activating AKT

Ma, Ping; Tang, Wei‐Guo; Hu, Jinwu; Hao, Ying; Xiong, Liangkun; Wang, Maoming; Líu, Hao; Bo, Wen-hui; Yu, Kaihuan

doi:10.1111/liv.14410

Cited by 22 publications

(16 citation statements)

References 35 publications

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“…EMT is reported to be an important cause of distal metastases of malignant tumors (37). Accumulating evidence has demonstrated that metastatic potential can be enhanced by activating EMT in numerous types of cancer, including HCC (38), BC (39) and cervical cancer (40). The present study revealed that overexpression of PFKP decreased the protein expression levels of E-cadherin, and increased the protein expression levels of N-cadherin and vimentin, whereas knockdown of PFKP had the opposite effect.…”

Section: Discussionsupporting

confidence: 42%

Platelet isoform of phosphofructokinase promotes aerobic glycolysis and the progression of non‑small cell lung cancer

Wang

Li²,

Zhang

2020

Mol Med Rep

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The platelet isoform of phosphofructokinase (PFKP) is a rate-limiting enzyme involved in glycolysis that serves an important role in various types of cancer. The aim of the present study was to explore the specific regulatory relationship between PFKP and non-small cell lung cancer (NSCLC) progression. PFKP expression in NSCLC tissues and corresponding adjacent tissues was detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical analysis. PFKP expression in human bronchial epithelial cells (16HBE) and NSCLC cells (H1299, H23 and A549) was also detected using RT-qPCR. Cell proliferation was detected by Cell Counting Kit-8 and colony formation assays. Transwell invasion and wound healing assays, and flow cytometry were used to detect cell invasion, migration and apoptosis, respectively. The expression levels of glycolysis-associated enzymes (hexokinase-2, lactate dehydrogenase A and glucose transporter-1), epithelial-mesenchymal transition-related proteins (N-cadherin, vimentin and E-cadherin) and apoptosis-related proteins (caspase-3 and B-cell lymphoma-2) were detected by western blotting. Glucose uptake, lactate production and the adenosine trisphosphate/adenosine diphosphate ratio were measured using the corresponding kits. The results of the present study demonstrated that PFKP expression was upregulated in NSCLC tissues and cells, and PFKP expression was related to lymph node metastasis and histological grade. In addition, overexpression of PFKP inhibited cell apoptosis, and promoted proliferation, migration, invasion and glycolysis of H1299 cells, whereas knockdown of PFKP had the opposite effects. In conclusion, PFKP inhibited cell apoptosis, and promoted proliferation, migration, invasion and glycolysis of NSCLC cells; these findings may lay the foundation for novel treatments of NSCLC.

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Section: Discussionsupporting

confidence: 42%

Platelet isoform of phosphofructokinase promotes aerobic glycolysis and the progression of non‑small cell lung cancer

Wang

Li²,

Zhang

2020

Mol Med Rep

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“…It is important to note that this analysis was performed using the UCSC Xena browser without the incorporation of the GTEx normal colon RNA-Seq data. A recent study showed that HSF4 expression was significantly upregulated in hepatocellular carcinoma (HCC) tissues, whereby targeting HSF4 reduced HCC cell growth and metastasis-associated phenotypes both in-vitro and in-vivo [109]. It was further demonstrated that HSF4 is involved in modulating the AKT-mTOR signaling pathway activation in a HIF1a-dependent manner [109].…”

Section: Cancermentioning

confidence: 99%

“…A recent study showed that HSF4 expression was significantly upregulated in hepatocellular carcinoma (HCC) tissues, whereby targeting HSF4 reduced HCC cell growth and metastasis-associated phenotypes both in-vitro and in-vivo [109]. It was further demonstrated that HSF4 is involved in modulating the AKT-mTOR signaling pathway activation in a HIF1a-dependent manner [109]. In fact, deregulations of the PI3K-AKT-mTOR signaling pathway have been widely implicated in cancer pathogenesis due to their central roles in promoting cell growth and regulating cellular metabolism and macromolecule biosynthesis [110][111][112].…”

Section: Cancermentioning

confidence: 99%

More Than Meets the Eye: Revisiting the Roles of Heat Shock Factor 4 in Health and Diseases

et al. 2021

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Cells encounter a myriad of endogenous and exogenous stresses that could perturb cellular physiological processes. Therefore, cells are equipped with several adaptive and stress-response machinery to overcome and survive these insults. One such machinery is the heat shock response (HSR) program that is governed by the heat shock factors (HSFs) family in response towards elevated temperature, free radicals, oxidants, and heavy metals. HSF4 is a member of this HSFs family that could exist in two predominant isoforms, either the transcriptional repressor HSFa or transcriptional activator HSF4b. HSF4 is constitutively active due to the lack of oligomerization negative regulator domain. HSF4 has been demonstrated to play roles in several physiological processes and not only limited to regulating the classical heat shock- or stress-responsive transcriptional programs. In this review, we will revisit and delineate the recent updates on HSF4 molecular properties. We also comprehensively discuss the roles of HSF4 in health and diseases, particularly in lens cell development, cataract formation, and cancer pathogenesis. Finally, we will posit the potential direction of HSF4 future research that could enhance our knowledge on HSF4 molecular networks as well as physiological and pathophysiological functions.

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“…As one of the hallmarks of malignancies, aberrant angiogenesis represents a form of niche construction in which cancer cells promote a local vascular ecology by delivering nutrients and growth factors, removing potentially toxic metabolites 5 . Previous studies have shown that the up‐regulation of hypoxia‐inducible factor (HIF)‐α activity promotes tumor‐associated angiogenesis and hence the proliferation and metastasis of cancer cells 6–8 . HIFs are heterodimers that consist of a constitutively expressed HIF‐1β subunit and an O 2 ‐regulated subunit, mainly including HIF‐1α and HIF‐2α 9 .…”

Section: Introductionmentioning

confidence: 99%

Effects of hypoxia‐inducible factor‐1α and hypoxia‐inducible factor‐2α overexpression on hepatocellular carcinoma survival: A systematic review with meta‐analysis

Ding

Dong

Chen

et al. 2021

J of Gastro and Hepatol

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Background and Aim The role of hypoxia‐inducible factor‐1α (HIF‐1α) and hypoxia‐inducible factor‐2α (HIF‐2α) has been implicated in the clinical prognosis of hepatocellular carcinoma (HCC), but the results remain controversial. We aim to investigate the association of HIF‐1α and HIF‐2α overexpression with the prognosis and clinicopathological features of HCC. Methods A systematic search was conducted in PubMed, Embase, Scopus, Web of Science, and Cochrane Library until June 20, 2020. Meta‐analysis was conducted to generate combined HRs with 95% confidence intervals (CI) for overall survival (OS) and disease‐free survival (DFS). Odds ratios (ORs) with 95% CI were also derived by fixed or random effect model. Results Twenty‐two studies involving 3238 patients were included. Combined data suggested that overexpression of HIF‐1α in HCC was not only correlated with poorer OS [HR = 1.75 (95% CI: 1.53–2.00)] and DFS [HR = 1.64 (95% CI: 1.34–2.00)] but was also positively associated with vascular invasion [OR = 1.83 (95% CI: 1.36–2.48)], tumor size [OR = 1.36 (95% CI: 1.12–1.66)], and tumor number [1.74 (95% CI: 1.34–2.25)]. In contrast, HIF‐2α overexpression was not associated with the prognosis and clinicopathological features of HCC. Conclusion Our data provided compelling evidence of a worse prognosis of HCC in HIF‐1α overexpression patients but not HIF‐2α overexpression ones.

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HSP4 triggers epithelial‐mesenchymal transition and promotes motility capacities of hepatocellular carcinoma cells via activating AKT

Cited by 22 publications

References 35 publications

Platelet isoform of phosphofructokinase promotes aerobic glycolysis and the progression of non‑small cell lung cancer

Platelet isoform of phosphofructokinase promotes aerobic glycolysis and the progression of non‑small cell lung cancer

More Than Meets the Eye: Revisiting the Roles of Heat Shock Factor 4 in Health and Diseases

Effects of hypoxia‐inducible factor‐1α and hypoxia‐inducible factor‐2α overexpression on hepatocellular carcinoma survival: A systematic review with meta‐analysis

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