School of Medicine, Northwest University, No. 229 Taibai North Road, Xi'an, Shaanxi, 710069, People's Republic of China.
Department of Oncology Surgery, Xi'an No.3 Hospital, the Affiliated Hospital of Northwest Universit, Xi'an, Shaanxi, 710018, People's Republic of China.
Biochem Genet. 2024 Feb;62(1):242-253. doi: 10.1007/s10528-023-10410-z. Epub 2023 Jun 16.
Pancreatic cancer remains the common cancer with the worst prognosis because of its late diagnosis and extensive metastasis. This study aimed to investigate the effects of GABRP on pancreatic cancer metastasis and the molecular mechanism. The expression of GABRP was measured using the quantitative real-time PCR and western blot. The biological behaviors of cancer cells were assessed using the cell counting kit-8, Transwell assay, and western blot. The regulation of GABRP on the MEK/ERK pathway was detected by western blot. The results indicated that GABRP was overexpressed in pancreatic cancer tissues and cells. Knockdown of GABRP suppressed cell viability, invasion, migration, and epithelial-mesenchymal transition (EMT), whereas GABRP overexpression facilitated these biological behaviors. Inactivation of the MEK/ERK pathway reversed the effects on cellular processes induced by GABRP. Moreover, silencing of GABRP inhibited tumor growth. In conclusion, GABRP promoted the progression of pancreatic cancer by facilitating cell metastasis and tumor growth via activating the MEK/ERK pathway. The findings suggest that GABRP has the potential to be a therapeutic target for the metastatic pancreatic cancer.
胰腺癌仍然是预后最差的常见癌症,因为其诊断较晚且广泛转移。本研究旨在探讨 GABRP 对胰腺癌转移的影响及其分子机制。采用实时定量 PCR 和 Western blot 检测 GABRP 的表达。采用细胞计数试剂盒-8、Transwell 检测和 Western blot 评估癌细胞的生物学行为。Western blot 检测 GABRP 对 MEK/ERK 通路的调节。结果表明,GABRP 在胰腺癌组织和细胞中过度表达。敲低 GABRP 抑制细胞活力、侵袭、迁移和上皮-间充质转化(EMT),而 GABRP 过表达促进这些生物学行为。MEK/ERK 通路失活逆转了 GABRP 诱导的细胞过程的影响。此外,沉默 GABRP 抑制肿瘤生长。总之,GABRP 通过激活 MEK/ERK 通路促进细胞转移和肿瘤生长,从而促进胰腺癌的进展。研究结果表明,GABRP 有可能成为转移性胰腺癌的治疗靶点。