Tumour Hypoxia and the Hypoxia-Inducible Transcription Factors: Key Players in Cancer Progression and Metastasis

Jögi, Annika

doi:10.1007/978-3-7091-1824-5_4

Cited by 6 publications

(2 citation statements)

References 269 publications

(292 reference statements)

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“…Two modules relating to metabolic processes were also found across a range of cancer types: a hypoxia module (e.g., VEGF, ADM ) 6,47–50 and an oxidative phosphorylation module (e.g., ATP5H, LAMTOR2 ) 9 . Metabolic adaptation to hypoxia in solid tumors, with increased glycolysis and induction of angiogenesis, has been implicated in cancer progression, drug resistance, invasion and metastasis 51,52 .…”

Section: Introductionmentioning

confidence: 97%

Recurrence of cancer cell states across diverse tumors and their interactions with the microenvironment

Barkley¹,

Moncada²,

Pour³

et al. 2021

Preprint

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While genetic tumor heterogeneity has long been recognized, recent work has revealed significant variation among cancer cells at the epigenetic and transcriptional levels. Profiling tumors at the single-cell level in individual cancer types has shown that transcriptional heterogeneity is organized into cancer cell states, implying that diverse cell states may represent stable and functional units with complementary roles in tumor maintenance and progression. However, it remains unclear to what extent these states span tumor types, constituting general features of cancer. Furthermore, the role of cancer cell states in tumor progression and their specific interactions with cells of the tumor microenvironment remain to be elucidated. Here, we perform a pan-cancer single-cell RNA-Seq analysis across 15 cancer types and identify a catalog of 16 gene modules whose expression defines recurrent cancer cell states, including 'stress', 'interferon response', 'epithelial-mesenchymal transition', 'metal response', 'basal' and 'ciliated'. Using mouse models, we find that induction of the interferon response module varies by tumor location and is diminished upon elimination of lymphocytes. Moreover, spatial transcriptomic analysis further links the interferon response in cancer cells to T cells and macrophages in the tumor microenvironment. Our work provides a framework for studying how cancer cell states interact with the tumor microenvironment to form organized systems capable of immune evasion, drug resistance, and metastasis.

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Section: Introductionmentioning

confidence: 97%

Recurrence of cancer cell states across diverse tumors and their interactions with the microenvironment

Barkley¹,

Moncada²,

Pour³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…However, altered metabolism is a hallmark of cancer, and metabolic reprogramming in cancer cells is seen in the main pathways of central carbon metabolism [214]. Different cancers are characterised by an intra-tumour hypoxia resulting from deregulated cell proliferation [215]. Tumour hypoxia is associated with poor prognosis and resistance to therapy [216].…”

Section: Respiration and Ph Imbalancementioning

confidence: 99%

Multifactorial Distress, the Warburg Effect, and Respiratory and pH Imbalance in Cancer Development

Drochioiu

2023

Stresses

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Oncogenes are thought to play an important role in aberrant regulation of growth factors, which is believed to be an initiation event of carcinogenesis. However, recent genetic and pharmacological studies have shown that the Warburg effect (WE) is needed for tumour growth. It refers to extensively studied aerobic glycolysis over the past decade, although its impact on cancer remains unclear. Meanwhile, a large body of evidence has indicated that oxidative stress (OS) is connected with the occurrence and progression of various forms of cancer. Psychosocial factors (PSF), such as chronic depression, sadness, stressful life experiences, stress-prone personality, and emotional distress or poor quality of life affect the immune system and contribute to cancer outcomes. Here, we examine the relationship between WE, OS, PSF, metal ions, other carcinogens, and the development of different cancers from the viewpoint of physiological and biochemical mechanisms.

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Endorsing cellular competitiveness in aberrant epithelium of oral submucous fibrosis progression: neighbourhood analysis of immunohistochemical attributes

Anura

Kazi

Pal³

et al. 2018

Histochem Cell Biol

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Epithelial abnormality during the transformation of oral submucous fibrosis (OSF) into oral squamous cell carcinoma has been well studied and documented. However, the differential contribution of atrophy and hyperplasia for malignant potentiality of OSF is yet to be resolved. Existing diagnostic conjectures lack precise diagnostic attributes which may be effectively resolved by substantiation of specific molecular pathology signatures. Present study elucidates existence of cellular competitiveness in OSF conditions using computer-assisted neighbourhood analysis in quantitative immunohistochemistry (IHC) framework. The concept of field cancerization was contributory in finding correspondence among neighbouring cells of epithelial layers with reference to differential expression of cardinal cancer-related genes [c-Myc (oncogene), p53 (tumour suppressor), and HIF-1α (hypoxia regulator)] which are known to be important sensors in recognizing cellular competitive interface. Our analyses indicate that different states of OSF condition may be associated with different forms of competitiveness within epithelial neighbouring cells which might be responsible to shape the present and future of the pre-malignant condition. Analytical findings indicated association of atrophic epithelium with stress-driven competitive environment having low c-Myc, high-p53, and stable HIF-1α (the looser cells) which undergo apoptosis. Whereas, the cells with high c-Myc (winner cells) give rise to hyperplastic epithelium via possible mutation in p53. The epithelial dysplasia plausibly occurs due to clonal expansion of c-Myc and p53 positive supercompetitor cells. Present study proposes quantitative IHC along with neighbourhood analysis which might help us to dig deeper on to the interaction among epithelial cell population to provide a better understanding of field cancerization and malignant transformation of pre-malignancy.

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Tumour Hypoxia and the Hypoxia-Inducible Transcription Factors: Key Players in Cancer Progression and Metastasis

Cited by 6 publications

References 269 publications

Recurrence of cancer cell states across diverse tumors and their interactions with the microenvironment

Recurrence of cancer cell states across diverse tumors and their interactions with the microenvironment

Multifactorial Distress, the Warburg Effect, and Respiratory and pH Imbalance in Cancer Development

Endorsing cellular competitiveness in aberrant epithelium of oral submucous fibrosis progression: neighbourhood analysis of immunohistochemical attributes

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