Notch-1 knockdown suppresses proliferation, migration and metastasis of salivary adenoid cystic carcinoma cells

Abstract

BackgroundNotch-1 promotes invasion and metastasis of cancer cells but its role in salivary adenoid cystic carcinoma (SACC) remains unelucidated. Here, we sought to investigate the effect of Notch-1 knockdown on the invasion and metastasis of SACC cells.MethodsStable ACC-M cells whose Notch-1 was silenced by lentiviral vectors were established. Cellular proliferation was evaluated by the MTT assays and clonogenic assays, apoptosis by flow cytometry and the migration of ACC-M cells by Transwell assays. Metastasis was evaluated by examining the number of lung nodules in Balb⁄c nu⁄nu nude mice bearing subcutaneous SACC xenografts.ResultsOur MTT assay revealed that Notch-1 knockdown significantly suppressed the proliferation of ACC-M cells compared with non-infected or scrambled control cells. Clonogenic assays further showed that Notch-1 knockdown significantly suppressed the clonogenic growth of ACC-M cells (p < 0.01 vs. controls). Our flow cytometry demonstrated that Notch-1 knockdown was associated with a significantly higher proportion of late apoptotic and necrotic cells (p < 0.01 vs. controls). Transwell assays revealed that Notch-1 knockdown markedly reduced the migratory capacity of ACC-M cells (p < 0.01 vs. controls) and xenograft studies showed that the number of metastatic nodules in the lung surface was significantly lower in nude mice bearing xenografts with Notch-1 knockdown compared to those bearing control xenografts (p < 0.01 vs. controls).ConclusionNotch-1 knockdown suppresses the growth and migration of SACC cells in vitro and the metastasis of SACC cells in vivo. Notch-1 may be a new candidate target in SACC.

Highly Tumorigenic Diffuse Large B Cell Lymphoma Cells Are Produced by Coculture with Stromal Cells

“…At the same time, the Notch signaling pathway was highly activated in adherent lymphoma cells. We therefore concluded that Notch pathway activation correlates with tumor cell proliferation, as shown by previous studies [34, 35]. Regarding chemoresistance, lymphoma cells cultured alone were more sensitive to lymphoma cells from the coculture system, as previous studies indicated [36].…”

Breast cancer lung metastasis: Molecular biology and therapeutic implications

“…48 A study by Chen et al focusing on the role of Notch in salivary adenoid cystic carcinoma cells, found that knockdown of Notch-1 significantly inhibited the formation of metastatic lung nodules induced by EMT. 49 While it is unclear how the Notch signaling pathway regulates primary tumor cells disseminating to the lung, we speculate that it may play a critical role in the adaptation of breast cancer cells to metastatic niches. Notch signaling pathway may also interact with other signaling pathways to dictate the function and fate of breast cancer cells during the metastatic process.…”

microRNA-30b inhibits cell invasion and migration through targeting collagen triple helix repeat containing 1 in non-small cell lung cancer

“…To metastasize, a cancer cell must acquire abilities such as the capacity to colonize new tissue and evade immune surveillance, which must involve a broad spectrum of mechanisms. Gene expression profiling experiments have uncovered many genes potentially implicated in cancer invasion and metastasis [ 25 – 28 ]. Matrix metalloproteinases (MMPs), a family of zinc-ion dependent endopeptidases comprising more than 21 subtypes, have been widely accepted to play an important role on cancer invasion or metastasis [ 29 – 32 ].…”