REPS2/POB1 is downregulated during human prostate cancer progression and inhibits growth factor signalling in prostate cancer cells

Expression and Clinical Significance of REPS2 in Human Esophageal Squamous Cell Carcinoma

“…Furthermore, REPS2 mRNA and protein expression levels in the HEEpic cell line were significantly higher than that in the ESCC cell lines. These findings were consistent with several other cancer reports (Oosterhoff et al, 2003; , 2004;Oosterhoff et al, 2005;Badway et al, 2011), meanwhile suggestting that REPS2 played an important role in the progression of ESCC as a tumour suppressor. However, the underlying mechanisms for the decreased expression of REPS2 in tumour are still incompletely understood but likely involved in growth factor receptormediated endocytosis and signalling through its influence on the Ral signalling pathway.…”

“…The activated Ral forms a complex with REPS2 through RalBP1 (a GTPaseactivating protein), whereas REPS2 could function as an inhibitor of the transport activity of RalBP1. Recently, it has been reported that increased REPS2 expression negatively affects EGF receptor internalisation and subsequent signaling, while loss of REPS2 expression in prostate cancer cells results in dysregulation of growth factor signaling and consequently in loss control of cell proliferation (Oosterhoff et al, 2003). Meanwhile, REPS2 isoform 2 downregulation has been observed during progression of prostate cancer from androgen to EGF dependency (Oosterhoff et al, 2003;Oosterhoff et al, 2005).…”

“…What is more, the binding of REPS2 to PAG2 inhibits cell migration (Oshiro et al, 2002). At present, REPS2 isoform 2 downregulation has been demonstrated in the progression of prostate cancer and the overexpression of REPS2 might serve as a useful biomarker for favorable prognosis in prostate and breast cancers (Oosterhoff et al, 2003;Oosterhoff et al, 2005;Doolan et al, 2009). On the contrary, REPS2 overexpression protects against dopaminergic cell death induced by paraquat (RodriguezRocha et al, 2012) and REPS2 is upregulated in clinical specimens of aggressive oral squamous cell carcinoma (Loudig et al, 2011).…”

“…Recently, it has been shown that overexpression of REPS2 and its binding with RalBP1 induce apoptosis and loss of REPS2 expression results in dysregulation of growth factor signaling in prostate cancer cells (Oosterhoff et al, 2003;Oosterhoff et al, 2005). Likewise, augmentation of cellular levels of REPS2 and Hsf-1 result in dramatic apoptosis in non-small cell lung cancer cell line H358 through RalBP1 inhibition (Singhal et al, 2008).…”

Self-regulatory role of 4-hydroxynonenal in signaling for stress-induced programmed cell death

“…The role of the HNE in transducing the membrane receptor-mediated signaling is further confirmed by our recent studies in which we show that the overexpression of RalBP1 in response to the increased level of HNE leads to increased endocytosis of the EGF receptor. RalBP1 along with the POB1 (partner of RalBP1) has been shown to be present in signal transduction complexes for membrane tyrosine-kinase receptors (such as EGF-R) and are phosphorylated [113][114][115][116]. The inhibition of endocytosis in the transport-deficient mutants of RalBP1 further supports the idea that the transport and endocytotic functions of RalBP1 are regulated by the cellular concentration of HNE and HNE-SG.…”