Nr5a2 promotes cancer stem cell properties and tumorigenesis in nonsmall cell lung cancer by regulating Nanog

In the present study, we have provided convincing evidence in vitro and in vivo demonstrating thatNr5a2 can induce lung cancer stem cells (CSC) properties and promote tumorigenesis and progression through transcriptional up ‐regulation of Nanog. AbstractLung cancer has the highest mortality rate due to late diagnosis and high incidence of metastasis. Cancer stem cells (CSCs) are a subgroup of cancer cells with self ‐renewal capability similar to that of normal stem cells (NSCs). While CSCs may play an important role in cancer progression, mechanisms underlying CSC self‐renewal and the relationship between self‐renewal of the NSCs and CSCs remain elusive. The orphan nuclear receptorNr5a2 is a transcriptional factor, and a regulator of stemness of embryonic stem cells and induced pluripotent stem cells. However, whetherNr5a2 regulates the self ‐renewal of lung CSCs is unknown. Here, we showed the diagnostic and prognostic values of elevatedNr5a2 expression in human lung cancer. We generated the mouse LLC ‐SD lung carcinoma CSC cellular model in whichNr5a2 expression was enhanced. Using the LLC ‐SD model, through transient and stable siRNA interference ofNr5a2 expression, we provided convincing evidence for a regulatory role ofNr5a2 in the maintenance of lung CSC self ‐renewal and stem cell properties in vitro. Further, using the syngeneic and orthotopic lung transplantation model, we elucidated augmented cancer biological properties associated withNr5a2 promotio...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research