Abstract
BackgroundDespite current advances in gastric cancer treatment, disease metastasis and chemo-resistance remain as major hurdles against better overall prognosis. Previous studies indicated that IGHG1 as well as -Catenin serve as important regulators of tumor cellular malignancy. Therefore, understanding detailed molecular mechanism and identifying druggable target will be of great potentials in future therapeutic development.MethodsSurgical tissues and gastric cancer cell lines were retrieved to evaluate IGHG1 expression for patients with or without lymph node/distal organ metastasis. Functional assays including CCK8 assay, Edu assay, sphere formation assay and transwell assay, wound healing assay, etc. were subsequently performed to evaluate the impact of IGHG1/-catenin axis on tumor cell proliferation, migration and chemo-resistance.ResultsGastric cancer tissues and tumor cell lines demonstrated significantly higher level of IGHG1. Functional study further demonstrated that IGHG1 promoted proliferative and migration as well as chemo-resistance of gastric cancer tumor cells. Further experiments indicated that IGHG1 activated AKT/GSK-3/-Catenin axis, which played crucial role in regulation of proliferative and chemo-resistance of gastric cancer cells.ConclusionThis study provided novel evidences that IGHG1 acted as oncogene by promotion of gastric cancer cellular proliferation, migration and chemo-resistance. Our research further suggested that IGHG1/AKT/GSK-3β/β-Catenin axis acted as novel pathway which regulated gastric cancer cellular malignant behavior. Our research might inspire future therapy development to promote overall prognosis of gastric cancer patients.
Highlights
Despite current advances in gastric cancer treatment, disease metastasis and chemo-resistance remain as major hurdles against better overall prognosis
IGHG1 expression level was significantly elevated in gastric cancer samples In this study, we firstly discovered IGHG1 expression pattern utilizing public bioinformatic analytic platform (GEPIA)
Subsequent western blot assay (Fig. 1D) on four pairs of gastric cancer and normal tissue samples as well as qRT-Polymerase chain reaction (PCR) study (Fig. 1E, F) on clinical gastric cancer samples in our clinical center suggested that IGHG1 protein and mRNA level were significantly elevated in cancer tissues (p < 0.001)
Summary
Despite current advances in gastric cancer treatment, disease metastasis and chemo-resistance remain as major hurdles against better overall prognosis. Previous studies indicated that IGHG1 as well as -Catenin serve as important regulators of tumor cellular malignancy. Understanding detailed molecular mechanism and identifying druggable target will be of great potentials in future therapeutic development. Gastric cancer stands as one of the most common cause of cancer mortality. According to the latest statistical data, gastric cancer remains as the fifth most common cancer. It has been clarified that east Asia, eastern Europe and south America are geographic hotspots for gastric cancer occurrence [1]. Age, salt intake, low vegetable intake are confirmed as risk factors for gastric cancer pathogenesis [2]. The main therapeutic strategy for early gastric cancer
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