Cancer Research Center, School of Medicine, Xiamen University, Xiamen, 361000, China.
Department of Pharmacy, Xiamen Mental Health Center, Xiamen Xianyue Hospital, Xiamen, 361000, China.
Oncol Res. 2023 Dec 28;32(2):361-371. doi: 10.32604/or.2023.043807. eCollection 2023.
The high mortality rate associated with gastric cancer (GC) has resulted in an urgent need to identify novel therapeutic targets for GC. This study aimed to investigate whether GAIP interacting protein, C terminus 1 (GIPC1) represents a therapeutic target and its regulating mechanism in GC. GIPC1 expression was elevated in GC tissues, liver metastasis tissues, and lymph node metastases. GIPC1 knockdown or GIPC1 blocking peptide blocked the platelet-derived growth factor receptor (PDGFR)/PI3K/AKT signaling pathway, and inhibited the proliferation and migration of GC cells. Conversely, GIPC1 overexpression markedly activated the PDGFR/PI3K/AKT signaling pathway, and promoted GC cell proliferation and migration. Furthermore, platelet-derived growth factor subunit BB (PDGF-BB) cytokines and the AKT inhibitor attenuated the effect of differential GIPC1 expression. Moreover, GIPC1 silencing decreased tumor growth and migration in BALB/c nude mice, while GIPC1 overexpression had contrasting effects. Taken together, our findings suggest that GIPC1 functions as an oncogene in GC and plays a central role in regulating cell proliferation and migration via the PDGFR/PI3K/AKT signaling pathway.
胃癌（GC）的高死亡率导致人们迫切需要寻找新的 GC 治疗靶点。本研究旨在探讨 GAIP 相互作用蛋白 C 端 1（GIPC1）是否代表 GC 中的治疗靶点及其调节机制。GIPC1 在 GC 组织、肝转移组织和淋巴结转移中表达升高。GIPC1 敲低或 GIPC1 阻断肽阻断血小板衍生生长因子受体（PDGFR）/PI3K/AKT 信号通路，并抑制 GC 细胞的增殖和迁移。相反，GIPC1 过表达显著激活 PDGFR/PI3K/AKT 信号通路，促进 GC 细胞增殖和迁移。此外，血小板衍生生长因子亚基 BB（PDGF-BB）细胞因子和 AKT 抑制剂减弱了 GIPC1 差异表达的作用。此外，GIPC1 沉默降低了 BALB/c 裸鼠中的肿瘤生长和迁移，而 GIPC1 过表达则产生相反的效果。综上所述，我们的研究结果表明，GIPC1 在 GC 中作为癌基因发挥作用，并通过 PDGFR/PI3K/AKT 信号通路在调节细胞增殖和迁移中发挥核心作用。
