Abstract 3365: Aldolase A induces invasion/metastasis of lung cancer through modulating HIF1-α and is a marker for poor clinical outcome

Abstract

Abstract The dysregulated metabolism is an emerging hallmark of cancer. However, little is known about the metabolic requirements during cancer progression. Therefore, identifying metabolic genes that are critical for supporting cancer invasion/metastasis may provide novel targets for cancer diagnosis and therapy. By analyzing gene expression and proteomic profile of invasive lung cancer cells CL1-5 and its parental counterpart CL1-0, we identified Aldolase A (ALDOA), an enzyme of glycolysis pathway, is overexpressed in CL1-5 and is significantly associated with disease recurrence in lung cancer patient microarray datasets. Moreover, HIF-1α was identified as the most significant transcription factor in ALDOA-recurrence gene signature by IPA upstream regulator analysis. Furthermore, Immunohistochemistry analysis confirmed the expression of ALDOA was markedly higher in lung cancer tumors than in normal lung. High ALDOA expression was found significantly associated with lymph node involvement and disease recurrence. Moreover, overexpression of ALDOA was significantly associated with poor outcome in both overall and disease-free survival. Knockdown of ALDOA expression was found to suppress invasion potentials in highly invasive lung cancer cell lines while complementary overexpression of ALDOA in poorly invasive cells promoted it in vitro and in vivo. ALDOA overexpression also accelerated glucose consumption, ATP utilization and lactate production. Knockdown of ALDOA expression in CL1-5 abolished HIF-1α expression with concurrent Mesenchymal-to-Epithelial Transition (MET). Moreover, IHC analysis shows an inverse correlation between ALDOA and E-cadherin and combination of high ALDOA and low E-Cadherin showed an unfavorable outcome, in a sharp contrast, compared to patients with low ALDOA and high E-cadherin. Here, we identified ALDOA as a critical glycolytic enzyme involved in lung cancer progression and may be a marker for poor clinical outcome. Citation Format: Yu-Chan Chang. Aldolase A induces invasion/metastasis of lung cancer through modulating HIF1-α and is a marker for poor clinical outcome. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3365. doi:10.1158/1538-7445.AM2014-3365