Role of ErbB Receptors in Cancer Cell Migration and Invasion

Abstract

Growth factors mediate their diverse biologic responses (regulation of cellular proliferation, differentiation, migration and survival) by binding to and activating cell-surface receptors with intrinsic protein kinase activity named receptor tyrosine kinases (RTKs). About 60 RTKs have been identified and can be classified into more than 16 different receptor families. Their activity is normally tightly controlled and regulated. Overexpression of RTK proteins or functional alterations caused by mutations in the corresponding genes or abnormal stimulation by autocrine growth factor loops contribute to constitutive RTK signaling, resulting in alterations in the physiological activities of cells. The ErbB receptor family of RTKs comprises four distinct receptors: the EGFR (also known as ErbB1/HER1), ErbB2 (neu, HER2), ErbB3 (HER3) and ErbB4 (HER4). ErbB family members are often overexpressed, amplified, or mutated in many forms of cancer, making them important therapeutic targets. EGFR has been found to be amplified in gliomas and non-small-cell lung carcinoma while ErbB2 amplifications are seen in breast, ovarian, bladder, non-small-cell lung carcinoma, as well as several other tumor types. Several data have shown that ErbB receptor family and its downstream pathway regulate epithelial-mesenchymal transition, migration, and tumor invasion by modulating extracellular matrix (ECM) components. Recent findings indicate that ECM components such as matrikines bind specifically to EGF receptor and promote cell invasion. In this review, we will present an in-depth overview of the structure, mechanisms, cell signaling, and functions of ErbB family receptors in cell adhesion and migration. Furthermore, we will describe in a last part the new strategies developed in anti-cancer therapy to inhibit ErbB family receptor activation.

Simvastatin induces cell cycle arrest and inhibits proliferation of bladder cancer cells via PPARγ signalling pathway

“…Many reports suggested PPARs modulation in cancer cells by either agonist or antagonist may be a potential treatment for metabolic diseases and cancer including BCa272829. Among those, the PPARγ pathway is particularly critical for the cancer stem cell properties of ErbB2-positive breast cancer cells3031, and has been reported to inhibit of ErbB activity in human breast cancer cells32.…”

Oridonin enhances in vitro anticancer effects of lentinan in SMMC‑7721 human hepatoma cells through apoptotic genes

“…Studies have shown that growth factors such as EGF promote the proliferation of stem cells and maintain the balance of normal cells (27). EGFR is a member of the ErbB receptor family on the cell surface, which is involved in cellular processes, including proliferation, growth, migration and invasion (28). Studies have also found that EGFR adjusts EGF-mediated cancer cell proliferation through saliva acidification (28,29).…”

“…EGFR is a member of the ErbB receptor family on the cell surface, which is involved in cellular processes, including proliferation, growth, migration and invasion (28). Studies have also found that EGFR adjusts EGF-mediated cancer cell proliferation through saliva acidification (28,29). In addition, EGFR inhibitors were shown to induce cancer cells to express UL16 binding protein 1 in order to enhance their sensitivity to natural killer cells (29).…”

ErbB2 Receptor in Breast Cancer: Implications in Cancer Cell Migration, Invasion and Resistance to Targeted Therapy

“…At the cellular level, the transition from noninvasive to invasive status is characterized by loss of the epithelial characteristics such as expression of cytokeratins and E-cadherin and gain of mesenchymal traits like vimentin, ibronectin and N-cadherin through a process that is known as epithelial to mesenchymal transition (EMT) [32]. EMT promotes cancer progression by allowing cancer cells to acquire invasive properties, to metastasize and also to acquire stem cell properties [33,34]. Interestingly, these cells that have acquired stem cell properties are characterized by increased expression of EMT genes, such as FoxC2, Zeb and N-cadherin [35,36].…”