The Relationship Between FEZ1/LZTS1and Breast Cancer Invasion、Metastasis And Chemosensitivity

Aims:FEZ1/LZTS1(LZTS1) is a tumor suppressor gene on chromosome8p22that is frequently altered in human cancers of different histotypes. In this study, we aim to investigate the function of LZTS1in breast cancer invasion and metastasis, and discuss its relationship with chemosensitivity in breast cancer.Materials and methods:Using gene transfection techniques, the LZTS1gene was re-expression in breast cancer MDA-MB-231cell line in which I ZTS1loss expression, then select the MDA-MB-231monoclonal cell lines stably express LZTS1to observe its impact on cell proliferation, migration and invasion. For further research LZTS1response to chemotherapeutic drugs, MTT test was used to detect the sensitivity of LZTS1expression to commonly used breast cancer drug paclitaxel (paclitaxel, PAC), epirubicin (epirubicin, EPI), cisplatin (cis-diamminedichloroplatinum, CDDP), vinorelbine (Navelbine, NVB) and5-fluorouracil (5-fluorouracil,5-FU); Animal experiments test the LZTS1expression response to paclitaxel in SCID nude mice; Expression of LZTS1were test in breast cancer patients before and after chemotherapy to invastigate its relationship with the chemotherapy drug reactions; In vitro primary cell culture of breast cancer Collagen gel droplet drug sensitivity test(CD-DST) was used to test relationship of LZTS1and chemotherapy drug sensitivityResults:1. In vitro expression of LZTS1can significantly inhibite breast cancer cell line MDA-MB-231migration, proliferation and infiltration.2. In vitro MDA-MB-231cells stably transfected LZTS1gene, increase drug sensitivity of paclitaxel and navelbine. 3. Animal experiments show that MDA-MB-231cells stably transfected LZTS1gene are more sensitive to paclitaxel than the empty vector group.4. Breast cancer patients with high LZTS1expression weremore sensitivve to the drug paclitaxel and navelbine. LZTS1can predict breast cancer response to chemotherapy with paclitaxel.Conclusions:LZTS1is a potential breast cancer suppressor gene. LZTS1protein expression decrease/deletion can promote breast cancer cell invasion and metastasis; LZTS1gene function recovery can inhibit tumor cell migration and invasion; LZTS1can predict the sensitivity of paclitaxel and navelbine, may be a new target to guide individual chemotherapy treatment.