Abstract
Although targeted therapy has improved the survival rates in the last decade, non-small-cell lung cancer (NSCLC) is still the most common cause of cancer-related death. The challenge of identifying new targets for further effective therapies still remains. The FAMily with sequence similarity 83 (FAM83) members have recently been described as novel oncogenes in numerous human cancer specimens and shown to be involved in epidermal growth factor receptor (EGFR) signaling. Here, gene expression of FAM83A and B was analyzed in a cohort of 362 NSCLC patients using qPCR. We further investigated relations in expression and their prognostic value. Functional assays in NSCLC cell lines were performed to evaluate FAM83A and B involvement in proliferation, anchorage-independent growth, migration, and the EGFR pathway. We observed a highly increased gene expression level of FAM83A (ø = 68-fold) and FAM83B (ø = 20-fold) which resulted in poor survival prognosis (p < 0.0001 and p = 0.002). Their expression was influenced by EGFR levels, pathway signaling, and mutation status. Both genes affected cell proliferation, and FAM83A depletion resulted in reduced migration and anchorage-independent growth. The results support the hypothesis that FAM83A and B have different functions in different histological subtypes of NSCLC and might be new therapeutic targets.
Highlights
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related death worldwide [1]
FAM83A and B Are Highly Overexpressed in non-small-cell lung cancer (NSCLC)
FAM83B was analyzed by quantitative polymerase chain reaction (qPCR) in a cohort including 362 patients (Table 1)
Summary
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related death worldwide [1]. The plasticity of cancer cells and the compensatory activation of downstream pathways often result in resistance to targeted therapies [6,7]. FAM83A and B proteins have been identified as possible key regulators in the EGFR pathway in breast cancer cells, leading to the development of resistance to TKIs [7,12,13]. The biological role of FAM83A and B in cancer cells, especially in NSCLC, still remains unclear, while a detailed understanding is critical to develop novel therapeutic approaches. We investigated the expression and function of FAM83A and B in NSCLC in general and in relation to the EGFR pathway. The analyses revealed that both genes might serve as effective new diagnostic and prognostic biomarkers in NSCLC, with severe impact on various biological functions
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