GPER1 links estrogens to centrosome amplification and chromosomal instability in human colon cells

Bühler, Miriam; Fahrländer, Jeanine; Sauter, Alexander; Becker, Markus; Wistorf, Elisa; Steinfath, Matthias; Stolz, Ailine

doi:10.26508/lsa.202201499

Cited by 4 publications

(2 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In support of this hypothesis, GPER expression was shown to be upregulated and stimulated by MAPK signalling in mycotoxin-induced growth of colon cancer cells [187]. In addition, GPER can promote chromosomal instability in CRC, leading to neoplastic transformation and tumour development [188]. The impact of GPER signalling on angiogenesis may also be determinant in its tumour promoter actions [189,190].…”

Section: Oestrogen Signalling Via G Protein-coupled Oestrogen Recepto...mentioning

confidence: 87%

Sex Differences in Colon Cancer: Genomic and Nongenomic Signalling of Oestrogen

Harvey,

Harvey

2023

Genes

View full text Add to dashboard Cite

Colon cancer (CRC) is a prevalent malignancy that exhibits distinct differences in incidence, prognosis, and treatment responses between males and females. These disparities have long been attributed to hormonal differences, particularly the influence of oestrogen signalling. This review aims to provide a comprehensive analysis of recent advances in our understanding of the molecular mechanisms underlying sex differences in colon cancer and the protective role of membrane and nuclear oestrogen signalling in CRC development, progression, and therapeutic interventions. We discuss the epidemiological and molecular evidence supporting sex differences in colon cancer, followed by an exploration of the impact of oestrogen in CRC through various genomic and nongenomic signalling pathways involving membrane and nuclear oestrogen receptors. Furthermore, we examine the interplay between oestrogen receptors and other signalling pathways, in particular the Wnt/β-catenin proliferative pathway and hypoxia in shaping biological sex differences and oestrogen protective actions in colon cancer. Lastly, we highlight the potential therapeutic implications of targeting oestrogen signalling in the management of colon cancer and propose future research directions to address the current gaps in our understanding of this complex phenomenon.

show abstract

Section: Oestrogen Signalling Via G Protein-coupled Oestrogen Recepto...mentioning

confidence: 87%

Sex Differences in Colon Cancer: Genomic and Nongenomic Signalling of Oestrogen

Harvey,

Harvey

2023

Genes

View full text Add to dashboard Cite

show abstract

“…98 Together, defects in centrosome duplication and separation contribute to the formation of monopolar and multipolar spindles, which are frequently observed in human tumors and are associated with CIN. [168][169][170][171][172][173] Microtubule kinetochore attachment error. The process of spindle microtubules binding to kinetochores is asynchronous and stochastic, occurring at different times and in a random manner.…”

Section: Causes Of Cinmentioning

confidence: 99%

The two sides of chromosomal instability: drivers and brakes in cancer

Hosea,

Hillary,

Naqvi

et al. 2024

Sig Transduct Target Ther

View full text Add to dashboard Cite

Chromosomal instability (CIN) is a hallmark of cancer and is associated with tumor cell malignancy. CIN triggers a chain reaction in cells leading to chromosomal abnormalities, including deviations from the normal chromosome number or structural changes in chromosomes. CIN arises from errors in DNA replication and chromosome segregation during cell division, leading to the formation of cells with abnormal number and/or structure of chromosomes. Errors in DNA replication result from abnormal replication licensing as well as replication stress, such as double-strand breaks and stalled replication forks; meanwhile, errors in chromosome segregation stem from defects in chromosome segregation machinery, including centrosome amplification, erroneous microtubule–kinetochore attachments, spindle assembly checkpoint, or defective sister chromatids cohesion. In normal cells, CIN is deleterious and is associated with DNA damage, proteotoxic stress, metabolic alteration, cell cycle arrest, and senescence. Paradoxically, despite these negative consequences, CIN is one of the hallmarks of cancer found in over 90% of solid tumors and in blood cancers. Furthermore, CIN could endow tumors with enhanced adaptation capabilities due to increased intratumor heterogeneity, thereby facilitating adaptive resistance to therapies; however, excessive CIN could induce tumor cells death, leading to the “just-right” model for CIN in tumors. Elucidating the complex nature of CIN is crucial for understanding the dynamics of tumorigenesis and for developing effective anti-tumor treatments. This review provides an overview of causes and consequences of CIN, as well as the paradox of CIN, a phenomenon that continues to perplex researchers. Finally, this review explores the potential of CIN-based anti-tumor therapy.

show abstract

17β-estradiol in colorectal cancer: friend or foe?

Wu,

Xiao,

Wang

et al. 2024

Cell Commun Signal

View full text Add to dashboard Cite

Colorectal cancer (CRC) is a common gastrointestinal malignancy with higher incidence and mortality rates in men compared to women, potentially due to the effects of estrogen signaling. There is substantial evidence supporting the significant role of 17β-Estradiol (E2) in reducing CRC risk in females, although this perspective remains debated. E2 has been demonstrated to inhibit CRC cell proliferation and migration at the cellular level by enhancing DNA mismatch repair, modulating key gene expression, triggering cell cycle arrest, and reducing activity of migration factors. Furthermore, E2 contributes to promote a tumor microenvironment unfavorable for CRC growth by stimulating ERβ expression, reducing inflammatory responses, reversing immunosuppression, and altering the gut microbiome composition. Conversely, under conditions of high oxidative stress, hypoxia, and nutritional deficiencies, E2 may facilitate CRC development through GPER-mediated non-genomic signaling. E2’s influence on CRC involves the genomic and non-genomic signals mediated by ERβ and GPER, respectively, leading to its dual roles in anticancer activity and carcinogenesis. This review aims to summarize the potential mechanisms by which E2 directly or indirectly impacts CRC development, providing insights into the phenomenon of sexual dimorphism in CRC and suggesting potential strategies for prevention and treatment. Graphical Abstract

show abstract

GPER1 links estrogens to centrosome amplification and chromosomal instability in human colon cells

Cited by 4 publications

References 92 publications

Sex Differences in Colon Cancer: Genomic and Nongenomic Signalling of Oestrogen

Sex Differences in Colon Cancer: Genomic and Nongenomic Signalling of Oestrogen

The two sides of chromosomal instability: drivers and brakes in cancer

17β-estradiol in colorectal cancer: friend or foe?

Contact Info

Product

Resources

About