Enhanced expression of SOS1 is detected in prostate cancer epithelial cells from African-American men

Dritschilo,

doi:10.3892/ijo_00000388

Cited by 26 publications

(3 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, Son of Sevenless 1 (SOS1) is an activator of Ras/MAPK, which is overexpressed in AA prostate cancer cells. SOS1 increased levels caused higher cancer cell proliferation and migration through increased activation of ERK signaling pathways (Timofeeva et al, 2009). PI3K-AKT is one of the most important signaling pathways, which is differentially activated among different races and may modulate the mTOR pathway in several human cancers.…”

Section: Mtor/erk-1/2-associated Signaling Molecules and Racial Disparitymentioning

confidence: 99%

Racially Disparate Expression of mTOR/ERK-1/2 Allied Proteins in Cancer

Mishra

Charan

Verma

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Recent studies revealed that ethnic differences in mechanistic target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK-1/2) signaling pathways might be associated with the development and progression of different human malignancies. The African American (AA) population has an increased rate of cancer incidence and mortality compared to the Caucasian American (CA) population. Although the socioeconomic differences across different ethnic groups contribute to the disparity in developing different cancers, recent scientific evidence indicates the association of molecular and genetic variations in racial disparities of different human malignancies. The mTOR and ERK-1/2 signaling pathways are one of the well-known oncogenic signaling mechanisms that regulate diverse molecular and phenotypic aspects of normal as well as cancer cells in response to different external or internal stimuli. To date, very few studies have been carried out to explore the significance of racial disparity with abnormal mTOR and ERK-1/2 kinase signaling pathways, which may contribute to the development of aggressive human cancers. In this review, we discuss the differential regulation of mTOR and ERK-1/2 kinase signaling pathways across different ethnic groups, especially between AA and CA populations. Notably, we observed that key signaling proteins associated with mTOR and ERK-1/2 pathway including transforming growth factor-beta (TGF-β), Akt, and VEGFR showed racially disparate expression in cancer patients. Overall, this review article encompasses the significance of racially disparate signaling molecules related to mTOR/ERK1/2 and their potential in developing tailor-made anti-cancer therapies.

show abstract

Section: Mtor/erk-1/2-associated Signaling Molecules and Racial Disparitymentioning

confidence: 99%

Racially Disparate Expression of mTOR/ERK-1/2 Allied Proteins in Cancer

Mishra

Charan

Verma

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Microarray analyses of 69 clinically matched patients with prostate cancer demonstrated differences in gene expression profiles of prostate tumors from AA and CA men, particularly in genes related to tumor immunobiology ( 9 ). Our previous report of gene expression in prostate epithelial cells from AA and CA men show differences in the expression of genes affecting tumor aggressiveness and metastases using high-throughput microarray assays ( 8 ). These observations support primary epithelial cultures as a useful tool for discovering molecular mechanisms underlying health disparities in prostate cancer; however, the cultures permitted <5 passages, followed by cell senescence and cell death.…”

Section: Introductionmentioning

confidence: 99%

Novel Paired Normal Prostate and Prostate Cancer Model Cell Systems Derived from African American Patients

Jung

Kowalczyk

Hankins

et al. 2022

Cancer Research Communications

View full text Add to dashboard Cite

Prostate cancer is the most frequently diagnosed solid malignancy in men. African American (AA) men are at greater risk for developing prostate cancer, and experience higher mortality rates, as compared to Caucasian American (CA) men. However, mechanistic studies to understand this health disparity have been limited by the lack of relevant in vitro and in vivo models. There is an urgent need for preclinical cellular models to investigate molecular mechanisms underlying prostate cancer in AA men. We collected clinical specimens from radical prostatectomies of AA patients and established ten paired tumor-derived and normal epithelial cell cultures from the same donors, which were further cultivated to extend the growth under “conditional reprogramming (CR)”. Clinical and cellular annotations characterized these model cells as intermediate risk and predominantly diploid. Immunocytochemical analyses demonstrated variable expression levels of luminal (CK8) and basal (CK5, p63) markers in both normal and tumor cells. However, expression levels of TOPK, c-MYC, and N-MYC were markedly increased only in tumor cells. To determine cell utility for drug testing, we examined viability of cells following exposure to the anti-androgen (Bicalutamide) and two PARP-inhibitors (Olaparib and Niraparib) and observed decreased viability of tumor-derived cells as compared to viability of normal prostate derived cells.

show abstract

“…The current study found that expression of SOS1 and its downstream, JNK2, c-JUN, and MMP9, were induced by oxidative stress in HCC cells. Consistence with the study by Timofeeva et al, they showed that SOS1 was overexpressed in prostate cancer cells, and it was associated with increased cell migration and invasion (127). These data suggested that elevated SOS1 may be linked to enhanced aggressiveness of tumor cells.…”

mentioning

confidence: 53%

Epigenetic regulation of reactive oxygen species-induced tumor progression in hepatocellular carcinoma

Phoyen

View full text Add to dashboard Cite

Oxidative stress is a consequence of an imbalance of antioxidants and reactive species. The most common form of reactive species is derived from oxygen, called reactive oxygen species (ROS). ROS involve in pathogenesis of several diseases including cancers. Cancer genesis and progression are contributed through both genetic and epigenetic mechanisms. Histone modification, a post-translational modification at histone tails, is one of the epigenetic mechanisms known to participate in carcinogenesis and tumor progression. Although the ROS-induced histone modification alteration has been demonstrated in some cancers, the change in histone methylation and gene expression by ROS in hepatocellular carcinoma (HCC) is scarcely reported. This study aimed to investigate the effect of ROS on tumor progression via histone modification in HCC cell lines. Expression of inactive chromatin (H4K20me3, H3K9me3) and active chromatin (H3K4me3) marks and their clinical significance were also investigated. The result showed that ROS promoted epithelial-mesenchymal transition (EMT) in HCC cells, indicated by reduced expression of E-cadherin, and enhanced expression of ?-SMA and SNAIL. Cell migration, invasion, and colony formation were higher in HCC cells treated with ROS than the untreated controls. Co-treatment with antioxidant attenuated oxidative stress, inhibited EMT and decreased tumor progressivity in HCC cells exposed to H2O2. H4K20me3, H3K9me3, H3K4me3 and histone methyltransferases (SUV420H2, SUV39H1 and SMYD3) was upregulated in H2O2-treated HCC cells compared with the untreated controls. Chromatin immunoprecipitation-sequencing demonstrated that alteration of histone methylation (H4K20me3 and H3K4me3) by ROS was associated with upregulation of genes involved in DNA repair pathway (MRE11, BRCA1, MMS22L and RBBP8,) telomere maintenance (DCLRE1B, TERF1 and TERF2), and EMT pathway (SOS1 and RHOA) in HCC cells. The transcript expression of MRE11, BRCA1, MMS22L, RBBP8, DCLRE1B, TERF1 and TERF2 in HCC cells were increased following the H2O2 treatment. RBBP8 was selected to validate in the human HCC tissues, and it was overexpressed in the HCC tissues compared with the non-cancerous liver tissues. Expression of H4K20me3 was also higher in HCC tissues than the non-cancerous tissues. Elevated expression of H4K20me3 was associated with tumor recurrence and poor survival in HCC patients. In conclusion, ROS-induced oxidative stress promoted HCC progression through chromatin remodeling that subsequently upregulated genes related to EMT and DNA repairing pathways. H4K20me3 was upregulated in the HCC tissues, and its overexpression was clinically associated with the poor prognosis. The findings suggested that histone methylation, specifically H4K20me3, might be a promising marker for HCC prognosis, and it could be a target for development of HCC therapeutic agent in the future.

show abstract

Enhanced expression of SOS1 is detected in prostate cancer epithelial cells from African-American men

Cited by 26 publications

References 39 publications

Racially Disparate Expression of mTOR/ERK-1/2 Allied Proteins in Cancer

Racially Disparate Expression of mTOR/ERK-1/2 Allied Proteins in Cancer

Novel Paired Normal Prostate and Prostate Cancer Model Cell Systems Derived from African American Patients

Epigenetic regulation of reactive oxygen species-induced tumor progression in hepatocellular carcinoma

Contact Info

Product

Resources

About