Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells

Silva, Valdenizia R.; Santos, Luciano de S.; Dias, Rosane Borges; Quadros, Claudio Almeida; Bezerra, Daniel P.

doi:10.1002/cac2.12235

Cited by 55 publications

(19 citation statements)

References 349 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It responds to tissue turnover and regeneration via regulating stem cells, including hematopoietic stem cells 24 , embryonic stem cells 25 , as well as ISCs 26 . It is also a maintainer for cancer stem cells and promoter for multiple cancers, such as colorectal cancer 27 . STAT5, consisting of the transcription activator STAT5A and STAT5B, is a positive contributor to ISCs and intestinal epithelial regeneration in the dextran sulfate sodium (DSS)-induced colitis, Clostridium difficile infection-induced Ileocolitis, and irradiation-induced intestinal injury mouse models 28 , 29 .…”

Section: Discussionmentioning

confidence: 99%

Jwa participates the maintenance of intestinal epithelial homeostasis via ERK/FBXW7-mediated NOTCH1/PPARγ/STAT5 axis and acts as a novel putative aging related gene

Li¹,

Li²,

Zhou³

et al. 2022

Int. J. Biol. Sci.

View full text Add to dashboard Cite

The intestinal epithelium is a rapid self-renewal and regenerated tissue of which the structural integrity is beneficial for maintaining health. The integrity of intestinal epithelium depends on the balance of cell proliferation, differentiation, migration, and the function of intestinal stem cells, which declines due to genetic defect or aging. Jwa participates in multiple cellular processes; it also responds to oxidative stress and repairs DNA damage. However, whether Jwa plays a role in maintaining the homeostasis of intestinal renewal and regeneration is not clear. In the present study, we firstly described that the deletion of Jwa disturbed the homeostasis of intestinal epithelial renewal and regeneration. Jwa deficiency promoted NOTCH1 degradation in the ERK/FBXW7-mediated ubiquitin-proteasome pathway, thus disturbing the PPARγ/STAT5 axis. These mechanisms might partially contribute to the reduction of intestinal stem cell function and alteration of intestinal epithelial cell lineage distribution, finally suppressing the renewal and regeneration of intestinal epithelium. Moreover, our results also revealed that Jwa was a novel putative aging related gene.

show abstract

Section: Discussionmentioning

confidence: 99%

Jwa participates the maintenance of intestinal epithelial homeostasis via ERK/FBXW7-mediated NOTCH1/PPARγ/STAT5 axis and acts as a novel putative aging related gene

Li¹,

Li²,

Zhou³

et al. 2022

Int. J. Biol. Sci.

View full text Add to dashboard Cite

show abstract

“…In addition, the mTOR and PI3K pathways can lead to resistance to cancer cell apoptosis and induce EMT [62]. Together, mTOR expression has been associated with poor prognosis in some types of cancer, so mTOR inhibitors could represent a therapeutic alternative in order to improve the effectiveness of current treatments [63].…”

Section: Growth Factorsmentioning

confidence: 99%

Metabolic Reprogramming in Cancer Cells: Emerging Molecular Mechanisms and Novel Therapeutic Approaches

Navarro

Ortega²,

Santeliz³

et al. 2022

Pharmaceutics

View full text Add to dashboard Cite

The constant changes in cancer cell bioenergetics are widely known as metabolic reprogramming. Reprogramming is a process mediated by multiple factors, including oncogenes, growth factors, hypoxia-induced factors, and the loss of suppressor gene function, which support malignant transformation and tumor development in addition to cell heterogeneity. Consequently, this hallmark promotes resistance to conventional anti-tumor therapies by adapting to the drastic changes in the nutrient microenvironment that these therapies entail. Therefore, it represents a revolutionary landscape during cancer progression that could be useful for developing new and improved therapeutic strategies targeting alterations in cancer cell metabolism, such as the deregulated mTOR and PI3K pathways. Understanding the complex interactions of the underlying mechanisms of metabolic reprogramming during cancer initiation and progression is an active study field. Recently, novel approaches are being used to effectively battle and eliminate malignant cells. These include biguanides, mTOR inhibitors, glutaminase inhibition, and ion channels as drug targets. This review aims to provide a general overview of metabolic reprogramming, summarise recent progress in this field, and emphasize its use as an effective therapeutic target against cancer.

show abstract

“…Aberrant Wnt/β-catenin signaling is central to sporadic CRC, in which approximately 80% of cases harboring APC gene mutations [ 91 ]. This mutation causes the accumulation of β-catenin in the nucleus, where it can upregulate the transcription of several target genes (e.g., AXIN2, SURVIVIN, ALDH, Cyclin D1) [ 92 ]. In contrast, the role of Wnt signaling in UC-CRC was not given much attention in the past, while recently it was found to be involved in tumor formation.…”

Section: Mechanisms Of Colorectal Cancer In Ulcerative Colitismentioning

confidence: 99%

Colorectal Cancer in Ulcerative Colitis: Mechanisms, Surveillance and Chemoprevention

Zhao

et al. 2022

Current Oncology

View full text Add to dashboard Cite

Patients with ulcerative colitis (UC) are at a two- to three-fold increased risk of developing colorectal cancer (CRC) than the general population based on population-based data. UC-CRC has generated a series of clinical problems, which are reflected in its worse prognosis and higher mortality than sporadic CRC. Chronic inflammation is a significant contributor to the development of UC-CRC, so comprehending the relationship between the proinflammatory factors and epithelial cells together with downstream signaling pathways is the core to elucidate the mechanisms involved in developing of CRC. Clinical studies have shown the importance of early prevention, detection and management of CRC in patients with UC, and colonoscopic surveillance at regular intervals with multiple biopsies is considered the most effective way. The use of endoscopy with targeted biopsies of visible lesions has been supported in most populations. In contrast, random biopsies in patients with high-risk characteristics have been suggested during surveillance. Some of the agents used to treat UC are chemopreventive, the effects of which will be examined in cancers in UC in a population-based setting. In this review, we outline the current state of potential risk factors and chemopreventive recommendations in UC-CRC, with a specific focus on the proinflammatory mechanisms in promoting CRC and evidence for personalized surveillance.

show abstract

Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells

Cited by 55 publications

References 349 publications

Jwa participates the maintenance of intestinal epithelial homeostasis via ERK/FBXW7-mediated NOTCH1/PPARγ/STAT5 axis and acts as a novel putative aging related gene

Jwa participates the maintenance of intestinal epithelial homeostasis via ERK/FBXW7-mediated NOTCH1/PPARγ/STAT5 axis and acts as a novel putative aging related gene

Metabolic Reprogramming in Cancer Cells: Emerging Molecular Mechanisms and Novel Therapeutic Approaches

Colorectal Cancer in Ulcerative Colitis: Mechanisms, Surveillance and Chemoprevention

Contact Info

Product

Resources

About