scholarly journals Antagonism between EGFR and Wingless signalling in the larval cuticle of Drosophila

Development ◽  
1997 ◽  
Vol 124 (16) ◽  
pp. 3209-3219 ◽  
Author(s):  
D. Szuts ◽  
M. Freeman ◽  
M. Bienz
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Critical Role ◽  
Growth Factor Receptor ◽  
Dominant Negative ◽  
Signalling Pathways ◽  
Embryonic Cells ◽  
Larval Cuticle ◽  
Epidermal Growth

Signalling by the epidermal growth factor receptor (EGFR) plays a critical role in the segmental patterning of the ventral larval cuticle in Drosophila: by expressing a dominant-negative EGFR molecule or Spitz, an activating ligand of EGFR, we show that EGFR signalling specifies the anterior denticles in each segment of the larval abdomen. We provide evidence that these denticles derive from a segmental zone of embryonic cells in which EGFR signalling activity is maximal. Within each segment, there is a competition between the denticle fate specified by EGFR signalling and the naked cuticle fate specified by Wingless signalling. The final pattern of the denticle belts is the product of this antagonism between the two signalling pathways. Finally, we show that the segmental zones of high EGFR signalling activity depend on bithorax gene function and that they account for the main difference in shape between abdominal and thoracic denticle belts.

Recent Advances on Epidermal Growth Factor Receptor as a Molecular Target for Breast Cancer Therapeutics

2020 ◽  
Vol 21 ◽  
Author(s):  
Swathi R. Shetty ◽  
Ragini Yeeravalli ◽  
Tanya Bera ◽  
Amitava Das
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Critical Role ◽  
Growth Factor Receptor ◽  
Type I ◽  
Egfr Inhibition ◽  
Epidermal Growth

: Epidermal growth factor receptor (EGFR), a type-I transmembrane protein with intrinsic tyrosine kinase activity is activated by peptide growth factors such as EGF, epigen, amphiregulin, etc. EGFR plays a vital role in regulating cell growth, migration, and differentiation in various tissue-specific cancers. It has been reported to be overexpressed in lung, head, and neck, colon, brain, pancreatic, and breast cancer that trigger tumor progression and drug resistance. EGFR overexpression alters the signaling pathway and induces cell division, invasion, and cell survival. Our prior studies demonstrated that EGFR inhibition modulates chemosensitivity in breast cancer stem cells thereby serving as a potential drug target for breast cancer mitigation. Tyrosine kinase inhibitors (Lapatinib, Neratinib) and monoclonal antibodies (Trastuzumab) targeting EGFR have been developed and approved by the US FDA for clinical use against breast cancer. This review highlights the critical role of EGFR in breast cancer progression and enumerates the various approaches being undertaken to inhibit aggressive breast cancers by suppressing the downstream pathways. Further, the mechanisms of action of potential molecules at various stages of drug development as well as clinically approved drugs for breast cancer treatment are illustrated.

scholarly journals Overcoming endocrine resistance in hormone receptor–positive breast cancer

2018 ◽  
Vol 25 ◽  
pp. 18 ◽  
Author(s):  
A. AlFakeeh ◽  
C. Brezden-Masley
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Endocrine Therapy ◽  
Endocrine Resistance ◽  
Growth Factor Receptor ◽  
Signalling Pathways ◽  
Epidermal Growth ◽  
Positive Breast Cancer

Endocrine therapy, a major modality in the treatment of hormone receptor (hr)–positive breast cancer (bca), has improved outcomes in metastatic and nonmetastatic disease. However, a limiting factor to the use of endocrine therapy in bca is resistance resulting from the development of escape pathways that promote the survival of cancer cells despite estrogen receptor (er)–targeted therapy. The resistance pathways involve extensive cross-talk between er and receptor tyrosine kinase growth factors [epidermal growth factor receptor, human epidermal growth factor receptor 2 (her2), and insulin-like growth factor 1 receptor] and their downstream signalling pathways—most notably pi3k/akt/mtor and mapk. In some cases, resistance develops as a result of genetic or epigenetic alterations in various components of the signalling pathways, such as overexpression of her2 and erα co-activators, aberrant expression of cell-cycle regulators, and PIK3CA mutations. By combining endocrine therapy with various molecularly targeted agents and signal transduction inhibitors, some success has been achieved in overcoming and modulating endocrine resistance in hr-positive bca. Established strategies include selective er downregulators, anti-her2 agents, mtor (mechanistic target of rapamycin) inhibitors, and inhibitors of cyclin-dependent kinases 4 and 6. Inhibitors of pi3ka are not currently a treatment option for women with hr-positive bca outside the context of clinical trial. Ongoing clinical trials are exploring more agents that could be combined with endocrine therapy, and biomarkers that would help to guide decision-making and maximize clinical efficacy. In this review article, we address current treatment strategies for endocrine resistance, and we highlight future therapeutic targets in the endocrine pathway of bca.

Epidermal Growth Factor Receptor Biology in Head and Neck Cancer

2006 ◽  
Vol 24 (17) ◽  
pp. 2666-2672 ◽  
Author(s):  
Shailaja Kalyankrishna ◽  
Jennifer R. Grandis
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Head And Neck ◽  
Critical Role ◽  
Growth Factor Receptor ◽  
Egfr Inhibitors ◽  
Treatment Modalities ◽  
Egfr Inhibition ◽  
Epidermal Growth

Epidermal growth factor receptor (EGFR) is overexpressed in several epithelial malignancies, including head and neck squamous cell carcinoma (HNSCC), which exhibits EGFR overexpression in up to 90% of tumors. EGFR ligands such as transforming growth factor alpha are also overexpressed in HNSCC. EGFR plays a critical role in HNSCC growth, invasion, metastasis and angiogenesis. However, EGFR inhibitors as monotherapy have yielded only modest clinical outcomes. Potential mechanisms for lack of response to EGFR inhibition in HNSCC include constitutive activation of signaling pathways independent of EGFR, as well as genetic aberrations causing dysregulation of the cell cycle. EGFR-directed therapy may be optimized by identifying and selecting those HNSCC patients most likely to benefit from EGFR inhibition. Resistance to EGFR inhibition may be circumvented by combination therapy employing EGFR inhibitors together with other treatment modalities.

scholarly journals The Critical Role of the Epidermal Growth Factor Receptor in Endochondral Ossification

2011 ◽  
Vol 26 (11) ◽  
pp. 2622-2633 ◽  
Author(s):  
Xianrong Zhang ◽  
Valerie A Siclari ◽  
Shenghui Lan ◽  
Ji Zhu ◽  
Eiki Koyama ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Endochondral Ossification ◽  
Critical Role ◽  
Growth Factor Receptor ◽  
Epidermal Growth

scholarly journals Stage-Sensitive Blockade of Pituitary Somatomammotrope Development by Targeted Expression of a Dominant Negative Epidermal Growth Factor Receptor in Transgenic Mice

2001 ◽  
Vol 15 (4) ◽  
pp. 600-613 ◽  
Author(s):  
Meejeon Roh ◽  
Andrew J. Paterson ◽  
Sylvia L. Asa ◽  
Edward Chin ◽  
Jeffrey E. Kudlow
Keyword(s):  
Gene Expression ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Transgenic Mice ◽  
Growth Factor Receptor ◽  
Dominant Negative ◽  
Egfr Signaling ◽  
Control Of Gene Expression ◽  
Epidermal Growth

Abstract The epidermal growth factor receptor (EGFR) and its ligands EGF and transforming growth factor-α (TGFα) are expressed in the anterior pituitary, and overexpression of TGFα in the lactotrope cells of the pituitary gland in transgenic mice results in lactotrope hyperplasia and adenomata, suggesting a role for EGFR signaling in pituitary cell proliferation. To address the role of EGFR signaling in pituitary development in vivo, we blocked EGFR signaling in transgenic mice using the dominant negative properties of a mutant EGFR lacking an intracellular protein kinase domain (EGFR-tr). We directed EGFR-tr expression to GH- and PRL- producing cells using GH and PRL promoters, and a tetracycline-inducible gene expression system, to allow temporal control of gene expression. EGFR-tr overexpression in GH-producing cells during embryogenesis resulted in dwarf mice with pituitary hypoplasia. Both somatotrope and lactotrope development were blocked. However, when EGFR-tr overexpression was delayed to the postnatal period either by directing its expression with the PRL promoter or by delaying the onset of induction with tetracycline in the GH cells, no specific phenotype was observed. Lactotrope hyperplasia during pregnancy also occurred normally in the PRL-EGFR-tr mice. These data suggest that EGFR signaling is required for the differentiation and/or maintenance of somatomammotropes early in pituitary organogenesis but not later in life. (Molecular Endocrinology 15: 600–613, 2001)

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