Regulation of Signaling from the Epidermal Growth Factor Family

Burgess, AW

doi:10.1021/acs.jpcb.2c04156

Cited by 13 publications

(9 citation statements)

References 149 publications

(233 reference statements)

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“…Because ERBB2 is the preferential binding partner of all other ERBBs [36] and ERBB3 cannot signal alone [37], we focused our attention on ERBB2 signaling during KSHV reactivation. The ERBB signaling cascades are complex [38, 39]. Therefore, we measured activation of a panel of substrates (Fig 6A) using a high-throughput, reverse-phase protein array approach under both latent and induced lytic replication conditions in control and ERBB2 depleted cells.…”

Section: Resultsmentioning

confidence: 99%

Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation

Olson

Kang

Ladha

et al. 2023

Preprint

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Kaposi's sarcoma-associated herpesvirus (KSHV) causes several human diseases including Kaposi’s sarcoma (KS), a leading cause of cancer in Africa and in patients with AIDS. KS tumor cells harbor KSHV predominantly in a latent form, while typically <5% contain lytic replicating virus. Because both latent and lytic stages likely contribute to cancer initiation and progression, continued dissection of host regulators of this biological switch will provide insights into fundamental pathways controlling the KSHV life cycle and related disease pathogenesis. Several cellular protein kinases have been reported to promote or restrict KSHV reactivation, but our knowledge of these signaling mediators and pathways is incomplete. We employed a polypharmacology-based kinome screen to identifiy specific kinases that regulate KSHV reactivation. Those identified by the screen and validated by knockdown experiments included several kinases that enhance lytic reactivation: ERBB2 (HER2 or neu), ERBB3 (HER3), ERBB4 (HER4), MKNK2 (MNK2), ITK, TEC, and DSTYK (RIPK5). Conversely, ERBB1 (EGFR1 or HER1), MKNK1 (MNK1) and FRK (PTK5) were found to promote the maintenance of latency. Mechanistic characterization of ERBB2 pro-lytic functions revealed a signaling connection between ERBB2 and the activation of CREB1, a transcription factor that drives KSHV lytic gene expression. These studies provided a proof-of-principle application of a polypharmacology-based kinome screen for the study of KSHV reactivation and enabled the discovery of both kinase inhibitors and specific kinases that regulate the KSHV latent-to-lytic replication switch.

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Section: Resultsmentioning

confidence: 99%

Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation

Olson

Kang

Ladha

et al. 2023

Preprint

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“…The results of the enrichment analysis exhibited in Table 3 that miR-146a was involved in many signaling pathways, such as the receptor activator of nuclear factor Kappa B (NF-κB) signaling pathway, which was implicated in cancer, inflammatory and autoimmune diseases, septic shock, and viral infections, [ 28 ] and epidermal growth factor receptor (EGFR) signaling pathway which might participate in cell growth, proliferation and differentiation. [ 29 ] As indicated in Table 3 , several diseases, especially myocardial infarction, were associated with miR-146a. Table 4 exhibited that miR-146a rs2910164 polymorphism was also related to prostate, endometrium, lung, and central nervous system cancers.…”

Section: Resultsmentioning

confidence: 99%

Association between microRNA-146a rs2910164 polymorphism and coronary heart disease: An updated meta-analysis

Bao¹,

Li²,

Wang³

et al. 2022

Medicine

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Background: Coronary heart disease (CHD) is one of the manifestations of atherosclerosis with a high morbidity rate. MicroRNA (miRNA)-146a rs2910164, a single nucleotide polymorphism, is associated with the progression of CHD risk. However, the results are controversial and uncertain. Therefore, an updated meta-analysis was conducted to evaluate the association between rs2910164 and CHD susceptibility.Methods: PubMed, Cochrane Library, EMBASE, Web of Science, China's National Knowledge Infrastructure, VIP, and Wan fang were searched for the eligible articles until April 30, 2022. The odds ratios (ORs) with 95% confidence interval (CIs) were calculated to assess the correlation. Bonferroni correction was utilized between multiple comparisons. Trial sequential analysis was performed to measure the required information size and assess the reliability of the meta-analysis results.Results: A total of 18 eligible studies, including 6859 cases and 8469 controls, were analyzed in our meta-analysis. After Bonferroni correction, we found that the G allele at rs2910164 was associated with significantly decreased CHD risk in the allelic model (OR = 0.86), homozygous model (OR = 0.79), and heterozygous model (OR = 0.89) in total population. In the subgroup analysis, the subjects containing the G allele and GG genotype were associated with a lower risk of CHD in the Chinese population, not the GG + CG and CG genotype. In addition, under the allelic, homozygous, heterozygous, and dominant models, miR-146a rs2910164 was at lower CHD risk in the large size population except in the recessive model. Conclusion:These results show that miR-146a rs2910164 might be associated with lower CHD susceptibility.Abbreviations: CAD = coronary artery disease, CHD = coronary heart disease, CI = confidence interval, HWE = Hardy-Weinberg equilibrium, IRAK-1 = interleukin-1 receptor-associated kinase 1, miRNA = microRNA, NF-κB = nuclear factor Kappa B, RIS = required information size, SNP = single nucleotide polymorphism, TRAF-6 = tumor necrosis factor receptor-associated factor 6, TSA = trial sequential analysis.

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“…EGFR is another member of the RTK family, activated by several ligands including TGF-α, AREG and EGF [163,164]. Together with its well-established role in liver regeneration [165], EGFR signaling is also involved in different stages of CLD.…”

Section: Tyrosine Kinase Receptors: Met and Egfrmentioning

confidence: 99%

New and Old Key Players in Liver Cancer

Cuesta,

Palao,

Bragado

et al. 2023

IJMS

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Liver cancer represents a major health problem worldwide with growing incidence and high mortality, hepatocellular carcinoma (HCC) being the most frequent. Hepatocytes are likely the cellular origin of most HCCs through the accumulation of genetic alterations, although hepatic progenitor cells (HPCs) might also be candidates in specific cases, as discussed here. HCC usually develops in a context of chronic inflammation, fibrosis, and cirrhosis, although the role of fibrosis is controversial. The interplay between hepatocytes, immune cells and hepatic stellate cells is a key issue. This review summarizes critical aspects of the liver tumor microenvironment paying special attention to platelets as new key players, which exert both pro- and anti-tumor effects, determined by specific contexts and a tight regulation of platelet signaling. Additionally, the relevance of specific signaling pathways, mainly HGF/MET, EGFR and TGF-β is discussed. HGF and TGF-β are produced by different liver cells and platelets and regulate not only tumor cell fate but also HPCs, inflammation and fibrosis, these being key players in these processes. The role of C3G/RAPGEF1, required for the proper function of HGF/MET signaling in HCC and HPCs, is highlighted, due to its ability to promote HCC growth and, regulate HPC fate and platelet-mediated actions on liver cancer.

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Regulation of Signaling from the Epidermal Growth Factor Family

Cited by 13 publications

References 149 publications

Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation

Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation

Association between microRNA-146a rs2910164 polymorphism and coronary heart disease: An updated meta-analysis

New and Old Key Players in Liver Cancer

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