RASEF is a Novel Diagnostic Biomarker and a Therapeutic Target for Lung Cancer

Abstract

Genome-wide gene expression profiling revealed that the Ras and EF-hand domain containing (RASEF) transcript was significantly transactivated in the majority of lung cancers. Using lung cancer cells, transient expression of RASEF promoted cell growth, whereas RASEF knockdown not only reduced its expression but resulted in growth suppression of the cancer cells. Immunohistochemical staining using tumor tissue microarrays consisting of 341 archived non-small cell lung cancers (NSCLC) revealed the association of strong RASEF positivity with poor prognosis (P ¼ 0.0034 by multivariate analysis). Mechanistically, RASEF interacted with extracellular signal-regulated kinase (ERK) 1/2 and enhanced ERK1/2 signaling. Importantly, inhibiting the interaction between RASEF and ERK1/2 using a cell-permeable peptide that corresponded to the ERK1/2-interacting site of RASEF, suppressed growth of lung cancer cells. This study demonstrates that elevated RASEF promoted cell growth via enhanced ERK signaling and is associated with poor prognosis of NSCLC.

Identification of key genes relevant to the prognosis of ER-positive and ER-negative breast cancer based on a prognostic prediction system

“…The expression of RASEF, which encodes a member of the Rab family of GTPases, was found to be higher in breast tumors than in cutaneous malignant melanoma lesions [15]. In addition, Oshita et al suggested that RASEF overexpression might promote lung cancer cell proliferation by enhancing extracellular signal-regulated kinase (ERK) 1/2 signaling and that RASEF might be a poor prognostic marker in lung cancer [16].…”

Near‐genomewide RNAi screening for regulators of BRAFV600E‐induced senescence identifies RASEF, a gene epigenetically silenced in melanoma

“…Clearly, a more definitive characterization of RASEF as a tumor suppressor will require in vivo models. Notably, RASEF has been previously reported to have differential functions depending on the cancer type; it has been attributed with a tumor‐suppressive function in myeloid leukemia (Nakamura et al., ), while it has an oncogenic function in lung cancer (Oshita et al., ). Our study is consistent with a model in which RASEF acts as a tumor suppressor in melanoma.…”

Rab GTPases: Emerging Oncogenes and Tumor Suppressive Regulators for the Editing of Survival Pathways in Cancer

“…Rab45 represents a novel diagnostic biomarker and a potential therapeutic target for lung cancer [70,71]. KD of Rab45 by siRNA results in a significant decrease in the cell growth of NSCLC [70]. Conversely, Rab45 has also been implicated as a tumor suppressor.…”