The ErbB Signaling Network and Its Potential Role in Endometrial Cancer

Abstract

Endometrial cancer (EC) is the second most common malignancy of the female reproductive system worldwide. The updated EC classification emphasizes the significant role of various signaling pathways such as PIK3CA-PIK3R1-PTEN and RTK/RAS/β-catenin in EC pathogenesis. Some of these pathways are part of the EGF system signaling network, which becomes hyperactivated by various mechanisms and participates in cancer pathogenesis. In EC, the expression of ErbB receptors is significantly different, compared with the premenopausal and postmenopausal endometrium, mainly because of the increased transcriptional activity of ErbB encoding genes in EC cells. Moreover, there are some differences in ErbB-2 receptor profile among EC subgroups that could be explained by the alterations in pathophysiology and clinical behavior of various EC histologic subtypes. The fact that ErbB-2 receptor expression is more common in aggressive EC histologic subtypes (papillary serous and clear cell) could indicate a future role of ErbB-targeted therapies in well-defined EC subgroups with overexpression of ErbB receptors.

Mechanisms and therapeutic targets of ErbB family receptors in hepatocellular carcinoma: a narrative review

“…Neuregulin 1 (NRG1) and NRG2 act as ligands that bind to ErbB3, causing a conformational change in ErbB3, thereby facilitating the dimerization, phosphorylation, and activation of signaling pathways ( 68 ). There are nine classical ligands capable of activating ErbB4, among which NRG3 and NRG4 are unique ( 69 , 70 ).…”

The landscape of circRNAs in gliomas temozolomide resistance: Insights into molecular pathways

“…A recent study by Liu et al demonstrated that exosomal circCABIN1 changes glioma cell response to TMZ by overactivating ErbB signaling pathway [ 142 ]. ErbB pathway participates in cell proliferation, differentiation and apoptosis, and its downstream members are highly expressed in various cancers [ [143] , [144] , [145] ]. Functions of ErbB pathway is closely connected with other signaling pathways such as PI3K and MAPK pathway, and all together enhance cancer cell stemness in tumor tissue [ 146 , 147 ].…”

Why Does Your Uterus Become Malignant? The Impact of the Microbiome on Endometrial Carcinogenesis

“…Other examples are ErbB receptors classified as a subclass of receptor tyrosine kinases and components of the EGF system signaling network in cells. The expression of ErbB receptors was reported to be significantly different in EC, compared with that in the premenopausal and postmenopausal endometrium [87][88][89]. ErbB-2 overexpression and ErbB-2 gene amplification were reported extensively within EC patients as indicators of a more aggressive disease with reduced response to treatment and less favorable outcomes (especially in patients with type II EC in the traditional classification) [87,[90][91][92].…”

“…The expression of ErbB receptors was reported to be significantly different in EC, compared with that in the premenopausal and postmenopausal endometrium [87][88][89]. ErbB-2 overexpression and ErbB-2 gene amplification were reported extensively within EC patients as indicators of a more aggressive disease with reduced response to treatment and less favorable outcomes (especially in patients with type II EC in the traditional classification) [87,[90][91][92]. The linkage between microbiome transcriptional activity and ErbB gene expression is worth further investigation due to the role of the EGF system in the regulation of endometrial cyclical growth and its associations with the widely described PIK3CA-PIK3R1-PTEN, RTK/RAS/ β-catenin signaling pathways.…”