HIF1-alpha functions as a tumor promoter in cancer-associated fibroblasts, and as a tumor suppressor in breast cancer cells

Chiavarina, Barbara; Whitaker‐Menezes, Diana; Migneco, G; Martinez‐Outschoorn, Ubaldo; Pavlides, Stephanos; Howell, Anthony; Tanowitz, Herbert B.; Casimiro, Mathew C.; Wang, Chenguang; Pestell, Richard G.; Grieshaber, Philip; Caro, Jaime; Sotgia, Federica; Lisanti, Michael P.

doi:10.4161/cc.9.17.12908

Cited by 204 publications

(191 citation statements)

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“…We have previously reported that mRNA for HIF‐1α, the another potent tumor activator,65 is upregulated in fibroblasts infected by H. pylori (cagA+vacA+) strain 10. HIF‐1α is known to induce transcription of more than 60 genes and to play an important role in CAFs activation and release of a great number of proangiogenic factors including SDF‐1, IL‐8, and VEGF35, 65 also examined in our present study.…”

Section: Discussionmentioning

confidence: 99%

“…HIF‐1α is known to induce transcription of more than 60 genes and to play an important role in CAFs activation and release of a great number of proangiogenic factors including SDF‐1, IL‐8, and VEGF35, 65 also examined in our present study. CAFs produce a variety of ECM proteins such as fibronectin, TNC, and collagens, the structural components that make up connective tissue and contribute to the dense fibrous nature of solid tumors 66, 67, 68, 69, 70, 71.…”

Section: Discussionmentioning

confidence: 99%

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Role of Helicobacter pylori infection in cancer‐associated fibroblast‐induced epithelial‐mesenchymal transition in vitro

et al. 2018

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BackgroundMajor human gastrointestinal pathogen Helicobacter pylori (H. pylori) colonizes the gastric mucosa causing inflammation and severe complications including cancer, but the involvement of fibroblasts in the pathogenesis of these disorders in H. pylori‐infected stomach has been little studied. Normal stroma contains few fibroblasts, especially myofibroblasts. Their number rapidly increases in the reactive stroma surrounding inflammatory region and neoplastic tissue; however, the interaction between H. pylori and fibroblasts remains unknown. We determined the effect of coincubation of normal rat gastric fibroblasts with alive H. pylori (cagA+vacA+) and H. pylori (cagA−vacA−) strains on the differentiation of these fibroblasts into cells possessing characteristics of cancer‐associated fibroblasts (CAFs) able to induce epithelial‐mesenchymal transition (EMT) of normal rat gastric epithelial cells (RGM‐1).Materials and MethodsThe panel of CAFs markers mRNA was analyzed in H. pylori (cagA+vacA+)‐infected fibroblasts by RT‐PCR. After insert coculture of differentiated fibroblasts with RGM‐1 cells from 24 up to 48, 72, and 96 hours, the mRNA expression for EMT‐associated genes was analyzed by RT‐PCR.ResultsThe mRNA expression for CAFs markers was significantly increased after 72 hours of infection with H. pylori (cagA+vacA+) but not H. pylori (cagA−vacA−) strain. Following coculture with CAFs, RGM‐1 cells showed significant decrease in E‐cadherin mRNA, and the parallel increase in the expression of Twist and Snail transcription factors mRNA was observed along with the overexpression of mRNAs for TGFβR, HGFR, FGFR, N‐cadherin, vimentin, α‐SMA, VEGF, and integrin‐β1.Conclusion Helicobacter pylori (cagA+vacA+) strain induces differentiation of normal fibroblasts into CAFs, likely to initiate the EMT process in RGM‐1 epithelial cell line.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Role of Helicobacter pylori infection in cancer‐associated fibroblast‐induced epithelial‐mesenchymal transition in vitro

et al. 2018

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“…In direct support of this hypothesis, genetic induction of mitochondrial dysfunction in cancer-associated fibroblasts dramatically promotes both local tumor growth and distant cancer cell metastasis. [12][13][14][15][16][17][18][19][20][21][22][23][24] Conversely, genetic amplification of mitochondrial biogenesis in epithelial cancer cells also promotes tumor growth, independently of neo-angiogenesis. 23,[25][26][27][28] Consistent with these pre-clinical findings, we have identified a series of new stromal biomarkers and related gene signatures that are characteristic of this type of lethal cancer metabolism.…”

Section: Introductionmentioning

confidence: 99%

Mitochondria “fuel” breast cancer metabolism: Fifteen markers of mitochondrial biogenesis label epithelial cancer cells, but are excluded from adjacent stromal cells

et al. 2012

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“…12,[31][32][33][34][35][36][37] The fact that HIF1 is involved in mitochondrial autophagy processes and, in this case, in the regulation of mitochondrial respiration is important. 2,38 It seems that HIF1 help to reduce the amount of toxic metabolic waste products, which should have an effect on the lifespan of cells or of a whole organism too. 39 …”

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confidence: 99%

The real face of HIF1α in the tumor process

et al. 2012

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HIF1-alpha functions as a tumor promoter in cancer-associated fibroblasts, and as a tumor suppressor in breast cancer cells

Cited by 204 publications

References 31 publications

Role of Helicobacter pylori infection in cancer‐associated fibroblast‐induced epithelial‐mesenchymal transition in vitro

Role of Helicobacter pylori infection in cancer‐associated fibroblast‐induced epithelial‐mesenchymal transition in vitro

Mitochondria “fuel” breast cancer metabolism: Fifteen markers of mitochondrial biogenesis label epithelial cancer cells, but are excluded from adjacent stromal cells

The real face of HIF1α in the tumor process

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