Over-expression of LRIG1 suppresses biological function of pituitary adenoma via attenuation of PI3K/AKT and Ras/Raf/ERK pathways in vivo and in vitro

Abstract

Pituitary adenomas (PAs) are well known as a common intracranial benign tumor, and a portion of PAs are refractory to current therapeutic methods. ErbB receptors family signaling pathway regulates the expression of PAs activation associated gene. Inhibition of epidermal growth factor receptor (EGFR) can inhibit proliferation of PAs. Leucine-rich repeats and immunoglobulin-like domains protein 1 ( LRIG1), a negative mediated gene of ErbB receptors family, plays a role in many tumors. However, there are seldom researches about the functional role of LRIG1 in PAs. The aim of this study is to explore the potential effect of LRIG1 and its regulating mechanism in PAs. First, we investigated the role of LRIG1 in cell migration, invasion of PAs with transfected LRIG1 or control. Then, we explored its impact on cell proliferation and apoptosis of PAs in vivo. To study the regulating mechanism of LRIG1, we examined the expression of molecular factor of PI3K/AKT and Ras/Raf/ERK pathway using Western blotting in vitro and RT-PCR in vitro and in vivo. It was found that LRIG1 over-expression inhibited cell migration, invasion and proliferation, and promoted apoptosis of PAs in vivo and in vitro. Furthermore, LRIG1 suppressed the expression of signaling of PI3K/AKT and Ras/Raf/ERK pathways in PAs. LRIG1, as a negative mediated gene of tumor, can inhibit biological function of PAs via inhibiting PI3K/AKT and Ras/Raf/ERK pathways, and it might be a new target for gene therapy of PAs.

LRIG1, a regulator of stem cell quiescence and a pleiotropic feedback tumor suppressor

“…Subsequent manipulation on LRIG1 expression demonstrated that LRIG1 inhibited glioma growth and aggressiveness by attenuating EGFR activation and downstream PI3K/AKT signaling pathway [ 79 - 81 ]. Similar effect was observed in pituitary adenoma [ 82 ]. Notably, LRIG1 destabilized EGFR vIII in GBM, dampened EGFR vIII oncogenic activity and inhibited EGFR vIII -driven GBM cell proliferation and invasion [ 9 ].…”

Src homology phosphotyrosyl phosphatase 2 mediates cisplatin-related drug resistance by inhibiting apoptosis and activating the Ras/PI3K/Akt1/survivin pathway in lung cancer cells

“…The phosphoinositol 3-kinase (PI3K/Akt) pathway is involved in cell survival, differentiation, proliferation, apoptosis and metastasis and is implicated in the pathogenesis of many tumors (24).…”

Serine peptidase inhibitor Kazal type III (SPINK3) promotes BRL‐3A cell proliferation by targeting the PI3K–AKT signaling pathway

“…Through in vitro and in vivo studies, Cheng et al found that the inhibition of EGFR activation in pituitary adenoma cells, via the leucine‐rich repeat immunoglobulin‐like domain 1 (LRIG1), decreased the expression of ERK genes. This indicated that EGFR could inhibit cell proliferation through the RAS–RAF–ERK pathway following the inactivation of EGFR (Cheng et al, ). Zhou et al () found that when EGFR was inhibited, it decreased cell proliferation and promoted cell apoptosis though the RAS–RAF–MEK–ERK signaling pathway (Zhou et al, ).…”