Proliferative signaling by ERBB proteins and RAF/MEK/ERK effectors in polycystic kidney disease.

Proliferative signaling by ERBB proteins and RAF/MEK/ERK effectors in polycystic kidney disease. Cell Signal. 2019 Dec 09;:109497 Authors: Parker MI, Nikonova AS, Sun D, Golemis EA Abstract A primary pathological feature of polycystic kidney disease (PKD) is the hyperproliferation of epithelial cells in renal tubules, resulting in formation of fluid-filled cysts. The proliferative aspects of the two major forms of PKD-autosomal dominant PKD (ADPKD), which arises from mutations in the polycystins PKD1 and PKD2, and autosomal recessive PKD (ARPKD), which arises from mutations in PKHD1-has encouraged investigation into protein components of the core cell proliferative machinery as potential drivers of PKD pathogenesis. In this review, we examine the role of signaling by ERBB proteins and their effectors, with a primary focus on ADPKD. The ERBB family of receptor tyrosine kinases (EGFR/ERBB1, HER2/ERBB2, ERBB3, and ERBB4) are activated by extracellular ligands, inducing multiple pro-growth signaling cascades; among these, activation of signaling through the RAS GTPase, and the RAF, MEK1/2, and ERK1/2 kinases enhance cell proliferation and restrict apoptosis during renal tubuloepithelial cyst formation. Characteristics of PKD include overexpression and mislocalization of the ERBB receptors and ligands, leading to enhanced activation and increased activity of downstream signaling proteins. The altered regulation of ERBBs and their effectors in PKD is influence...
Source: Cellular Signalling - Category: Cytology Authors: Tags: Cell Signal Source Type: research

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Breast cancer (BC) with overexpression and/or amplification of the Human Epidermal Growth Factor Receptor 2 (HER2-positive) represents 11-30% of all breast tumors[1]. HER2 positivity is defined today by immunohistochemistry (IHC) as complete and strong membrane staining (i.e. score of 3+) in ≥10% of cancer cells, and/or by in situ immunofluorescence (ISH) techniques as amplified using a HER2/CEP17 ratio cutoff of ≥ 2.0 and an average HER2 gene copy number ≥ 4.0 signals per cell[2]. This consensus definition is based on the methods and cutoffs used over the years in pivotal trials that led to the approval of trastu...
Source: Cancer Treatment Reviews - Category: Cancer & Oncology Authors: Tags: Systematic or Meta-analysis Studies Source Type: research
ConclusionIn the neoadjuvant setting, the pCR rate with the standard TCbHP  →  T-DM1+P regimen was numerically better than the TCbHP regimen alone and significantly better in patients with ER+. Personalization of the T-DM1+P regimen could serve as a reasonable approach to minimize toxicity while maintaining efficacy.Trial registration ID: UMIN-CTR: UMIN000014649.
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
ConclusionsDisease progression occurred intracranially more often than extracranially following resection of a solitary BCBM. In ER+ patients, postoperative hormonal therapy was associated with longer OS. Postoperative HER2-targeted therapy did not show survival benefit in HER2+ patients. These results should be validated in larger cohorts.
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
This study aimed to propose a new therapeutic target by exploring the regulating pathway of HER2. METHODS: Reverse transcription polymerase chain reaction (RT-PCR), western blot and immunohistochemistry staining were used respectively to detect the expression of HER2, Twist, E-cadherin and Fascin1 in both HER2 knockdown and overexpressed cell lines. Trans-well chamber assay and wound healing assay were used to detect the invasive ability of gastric cancer cells. The correlation between HER2 and Twist was analyzed based on specimens obtained from 118 patients with gastric cancer. RESULTS: HER2 silencing decreased th...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
CONCLUSION: The Erk signaling pathway may be crucially involved in the differentiation induction of breast cancer cells in vitro and in vivo. Collectively, our results suggest that the combination can probably serve as promising candidates for the development of novel therapeutic approaches for different types of breast cancer. PMID: 31934280 [PubMed]
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
Authors: Zheng J, Zhou T, Li F, Shi J, Zhang L Abstract Background: To investigate the differences of clinic-pathological features among ductal carcinoma in situ (DCIS), ductal carcinoma in situ with micro-invasion (DCIS-MI) and early invasive carcinoma (IDC) in stage T1.Methods: From January 2014 to December 2018, 308 cases DCIS, DCIS-MI 92 cases and 111 cases of T1a, 343 cases of T1b, and 1032 cases of T1c were investigated in a retrospective analysis. The population and clinic-pathological characteristics including age, menstrual status, surgical mode, lymph node status and molecular markers were compared in eac...
Source: Cancer Investigation - Category: Cancer & Oncology Tags: Cancer Invest Source Type: research
Conclusions The effectiveness and safety results of eribulin as the first- or second-line treatment were favorable. Thus, these suggest eribulin may be a first-line treatment candidate for patients with HER2-negative advanced breast cancer in Japan.
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research
ntamaria-Martinez Rüegg Membrane-associated guanylate kinase (MAGUK) with inverted domain structure-1 (MAGI1) is an intracellular adaptor protein that stabilizes epithelial junctions consistent with a tumor suppressive function in several cancers of epithelial origin. Here we report, based on experimental results and human breast cancer (BC) patients’ gene expression data, that MAGI1 is highly expressed and acts as tumor suppressor in estrogen receptor (ER)+/HER2− but not in HER2+ or triple negative breast cancer (TNBC). Within the ER+/HER2− subset, high MAGI1 expression associates...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Conditions:   Invasive Breast Cancer;   Triple Negative Breast Cancer;   ER-Negative Breast Cancer;   PR-Negative Breast Cancer;   HER2-negative Breast Cancer Intervention:   Drug: Sacituzumab Govitecan Sponsors:   Aditya Bardia;   Immunomedics, Inc. Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
More News: Clinical Trials | Cytology | HER2 | Polycystic Kidney Disease | Urology & Nephrology