Sam68 Promotes the Progression of Human Breast Cancer through inducing Activation of EphA3
CURRENT CANCER DRUG TARGETS
Authors: Chen, Xinxin; Zhang, Lehong; Kuang, Ziqiao; Zou, Ying; Tang, Tian; Zhang, Wangjian; Hu, Xiaowu; Xia, Ting; Cao, Tengfei; Jia, Haixia; Yuan, Min
Abstract
Background: Src associated with mitosis of 68 kDa (Sam68), is often highly expressed in human cancers. Overexpression of Sam68 has been shown to be correlated with poor survival prognosis in some cancer patients. However, little is known whether Sam68 plays a role in promoting metastasis in breast cancer. Materials and Methods: The expression of Sam68 protein in breast cancer tissue was detected by immunohistochemistry. Trans-well assay, wound-healing, real-time PCR and Western blotting analysis were used to detect the effect of Sam68 on promoting EMT or metastasis of breast cancer. Next-generation RNA sequencing was used to analyze genes that may be regulated by Sam68. Results: Sam68 plays a positive role in promoting breast cancer metastasis. Sam68 was found to be overexpressed in breast cancer along with lymph node metastasis. MMP-9 was also found to be overexpressed in breast cancer tissue and was correlated to the expression of Sam68 (P<0.01). Xenograft in NOD/SCID mice and in vitro experiments confirmed that the invasion and metastatic ability of breast cancer cells were regulated by Sam68. And EPHA3 could be up-regulated by Sam68 in breast cancer. Conclusion: High expression of Sam68 participates in breast cancer metastasis by up-regulating the EPHA3 gene.
Propofol affects the growth and metastasis of pancreatic cancer via ADAM8
PHARMACOLOGICAL REPORTS
Authors: Yu, Xiangdi; Shi, Jinshan; Wang, Xin; Zhang, Fangxiang
Abstract
Background Anesthesia is a major component of surgery and recently considered an important regulator of cell phenotypes. Here we aimed to investigate propofol, an anesthesia drug, in suppressing pancreatic cancer (PDAC), focusing on A disintegrin and metalloprotease 8, (ADAM8) as a molecular mediator. Methods Quantitative real-time PCR and western blot were used to assess the change of ADAM8 expression in Panc1 PDAC cells treated with 5 or 10 mu g/mL propofol, using cells treated with BB-94 inhibitor as controls. ADAM8 activity was measured through quantifying fluorescence release induced by PEPDAB013 decomposition. MTT assay, scratch wound assay and Matrigel invasion assay were used to investigate the proliferation, migration and invasion of the cells. Western blot and immunohistochemical analysis were used to quantify integrin beta 1, ERK1/2, MMP2 and MMP9 expression. Results Propofol and BB-94 reduced ADAM8 expression, cell proliferation and migration of Panc1 cells. Tumor growth was inhibited by propofol and BB-94, concomitant with downregulation of integrin beta 1, ERK1/2, MMP2 and MMP9. ADAM8 is downregulated by propofol, leading to inhibition of pancreatic cancer proliferation and migration. Conclusion Pancreatic tumor growth is also inhibited by propofol and BB-94, which is attributed to suppression of ERK/MMPs signaling.
COA
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