The EPH/Ephrin System in Colorectal Cancer

Abstract

The EPH/ephrin system constitutes a bidirectional signaling pathway comprised of a family of tyrosine kinase receptors in tandem with their plasma membrane-bound ligand (ephrins). Its significance in a wide variety of physiologic and pathologic processes has been recognized during the past decades. In carcinogenesis, EPH/ephrins coordinate a wide spectrum of pathologic processes, such as angiogenesis, vessel infiltration, and metastasis. Despite the recent advances in colorectal cancer (CRC) diagnosis and treatment, it remains a leading cause of death globally, accounting for 9.2% of all cancer deaths. A growing body of literature has been published lately revitalizing our scientific interest towards the role of EPH/ephrins in pathogenesis and the treatment of CRC. The aim of the present review is to present the recent CRC data which might lead to clinical practice changes in the future.

Angiogenesis in gastrointestinal stromal tumors: From bench to bedside

“…It’s contribution in GIST progression has been reviewed[ 56 ] but data about potential effects in GIST vascularization process are missing. Towards the same direction, the Eph/ephrin system has been investigated in carcinogenesis[ 57 , 58 ]. It would be of paramount importance an attempt to outline its contribution in GIST angiogenesis.…”

An Overview of the Molecular Cues and Their Intracellular Signaling Shared by Cancer and the Nervous System: From Neurotransmitters to Synaptic Proteins, Anatomy of an All-Inclusive Cooperation

“…The Eph receptors, with their ligands the Ephrins, are a large family of transmembrane proteins that were originally implicated in many neurological functions [ 173 , 174 ]. Eph/ephrin signaling is exceptionally complicated because of its bidirectional nature (with Ephs and ephrins interacting “in trans” from two different cells), and as a consequence Eph/ephrin have been shown to coordinate a plethora of tumor-related processes from angiogenesis, inflammation, vascular infiltration, and metastasis to tumor immunity [ 175 , 176 , 177 ]. To name a few examples, increased Eph/ephrin signaling is associated with tumor progression in melanoma [ 178 ], breast [ 179 ], prostate [ 180 ], and colorectal cancer [ 175 ].…”

“…Eph/ephrin signaling is exceptionally complicated because of its bidirectional nature (with Ephs and ephrins interacting “in trans” from two different cells), and as a consequence Eph/ephrin have been shown to coordinate a plethora of tumor-related processes from angiogenesis, inflammation, vascular infiltration, and metastasis to tumor immunity [ 175 , 176 , 177 ]. To name a few examples, increased Eph/ephrin signaling is associated with tumor progression in melanoma [ 178 ], breast [ 179 ], prostate [ 180 ], and colorectal cancer [ 175 ]. The Eph family member EPHA2 has recently been proposed as a negative prognostic factor in triple-negative breast cancer (TNBC) patients; moreover, EPHA2 may act as a precision therapeutic target for this challenging condition [ 181 ].…”

A comprehensive prognostic and immunological analysis of ephrin family genes in hepatocellular carcinoma

“…Substantial evidence indicates that ephrins play a vital role in tumor angiogenesis, invasion, metastasis, and tumor stemness maintenance ( Lodola et al, 2017 ). Many ephrin ligands have been shown to be upregulated in multiple tumors and associated with poor prognosis, such as lung adenocarcinoma ( Deng et al, 2021 ), breast cancer ( Kaenel et al, 2012 ), colorectal cancer ( Papadakos et al, 2022 ), prostate cancer ( Zhao et al, 2021 ), bladder cancer ( Mencucci et al, 2020 ), and other cancers ( Surawska et al, 2004 ). Lin et al (2021) reported that EFNA4 is highly expressed in cancer tissues and leads to poor prognosis in patients with HCC.…”