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FAS receptor regulates HNSCC cancer stemness ability and pulmonary metastasis through Notch pathway
Author(s) -
Chang WeiMin,
Hsiao Michael
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.496.15
Subject(s) - cancer research , metastasis , jag1 , biology , cancer stem cell , head and neck squamous cell carcinoma , notch signaling pathway , fas receptor , cancer , cd44 , hmga2 , lung cancer , signal transduction , medicine , pathology , microbiology and biotechnology , cell , head and neck cancer , apoptosis , programmed cell death , microrna , genetics , biochemistry , gene
Up to 80% of head and neck squamous cell carcinoma (HNSCC) distance metastasis is occurring in lung through seeding of circulating cancer stem cells. It is crucial to understand the genes that are involved in HNSCC pulmonary colonization which may provide an important therapy niche in treating HNSCC patients successfully. Here, we found the FAS receptor knockout SAS cells could diminished the in vitro stemness ability and completely abolished the HNSCC pulmonary colonization in the immunodeficiency NSG mice. Even pretreated with single dose of FAS neutralize antibody could also significantly reduce the lung colonies forming numbers in vivo. FAS knockout could also prevent the in vitro cell migration and invasion abilities in the Boyden chamber assay. Using the reporter assays of common oncogenic signaling pathways, our results showed that Notch, HIF1A, RhoA, and STAT1 were suppressed in the FAS knockout cells. Moreover, the microarray analysis revealed that FAS knockout could also decrease stemness gene expressions, such as XIST, WDR66, HMGA2, and the ligand of Notch, Jag1 expressions. These genes and pathways reversal and complementation assays were performed and confirmed that indeed Notch pathway is one of the major downstream pathways of FAS‐mediated HNSCC stemness signaling to promote lung cancer metastasis. Taken together, our study found the novel FAS‐XIST axis might be mediated through Jag1/Notch pathway that may be contributing to HNSCC patient's lung metastasis. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .