Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China; Institute of Biliary Tract Disease Research, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China.
Cancer Lett. 2016 Mar 28;372(2):239-50. doi: 10.1016/j.canlet.2016.01.008. Epub 2016 Jan 18.
LASP-1 is an actin-binding protein that regulates cytoskeletal dynamics and cell migration. LASP-1 was previously identified in a cDNA library from metastatic breast cancer samples. This protein has since been detected in multiple human cancers, including liver cancer, gastric cancer and pancreatic cancer. S100P is a small calcium-binding protein in the S100 protein family that regulates cellular, physiological and pathological processes in various cancers. However, the clinical significance of LASP-1 and S100P expression in gallbladder cancer (GBC) is not yet clear. In our study, we focused on the clinical significance, biological function and mechanism of LASP-1 in gallbladder cancer and detected LASP-1 and S100P overexpression in GBC tissues. The expression of LASP-1 was significantly correlated with poor prognosis in GBC patients (P < 0.05). Furthermore, down-regulation of LASP-1 expression resulted in the obvious inhibition of proliferation and migration and caused cell cycle arrest by down-regulating S100P via the PI3K/AKT pathway; in mice, tumor volume was significantly decreased. In conclusion, LASP-1 may act as an oncogene to regulate the expression of S100P to influence cellular functions in GBC. LASP-1 could serve as a genetic treatment target in GBC patients.
LASP-1 是一种肌动蛋白结合蛋白,可调节细胞骨架动力学和细胞迁移。LASP-1 最初是在转移性乳腺癌样本的 cDNA 文库中鉴定出来的。此后,该蛋白已在多种人类癌症中被检测到,包括肝癌、胃癌和胰腺癌。S100P 是 S100 蛋白家族中的一种小钙结合蛋白,可调节多种癌症中的细胞、生理和病理过程。然而,LASP-1 和 S100P 在胆囊癌(GBC)中的表达的临床意义尚不清楚。在我们的研究中,我们专注于 LASP-1 在胆囊癌中的临床意义、生物学功能和机制,并检测了 GBC 组织中 LASP-1 和 S100P 的过表达。LASP-1 的表达与 GBC 患者的不良预后显著相关(P < 0.05)。此外,下调 LASP-1 的表达导致通过 PI3K/AKT 通路下调 S100P 导致增殖和迁移的明显抑制,并引起细胞周期停滞;在小鼠中,肿瘤体积显著减小。总之,LASP-1 可能作为一种癌基因通过调节 S100P 的表达来影响 GBC 中的细胞功能。LASP-1 可以作为 GBC 患者的遗传治疗靶点。