SOSTDC1 inhibits bone metastasis in non-small cell lung cancer and may serve as a clinical therapeutic target

摘要

Bone metastasis occurs in ~40% patients with non?small cell lung cancer (NSCLC), resulting in serious morbidity and mortality. Sclerostin domain?containing protein?1 (SOSTDC1) has been demonstrated to be associated with the development and progression of multiple types of cancer. However, the role of SOSTDC1 in NSCLC bone metastasis remains unclear. In the present study, it was identified that SOSTDC1 was downregulated in NSCLC bone metastatic lesions compared with that in primary tumors, and low SOSTDC1 expression predicted poor prognosis for patients with NSCLC. Functionally, SOSTDC1 overexpression suppressed NSCLC cell proliferation, migration, invasion and cancer cell?induced osteoclastogenesis, while SOSTDC1 knockdown produced the opposite effect. In addition, a number of potential downstream target genes of SOSTDC1, which were demonstrated to be associated with tumor progression and bone metastasis, were identified in NSCLC cells by RNA deep sequencing and RT?qPCR assays. The results from the present study may provide useful insight for an improved understanding of the pathogenesis of NSCLC bone metastasis, and suggest that SOSTDC1 may be a potential prognostic biomarker and therapeutic target for NSCLC bone metastasis.