The inhibition of HeLa cells proliferation through SPARCL1 mediated by SPP1.

ABSTRACT

Secreted protein acidic and rich in cysteines-like 1 (SPARCL1) is implicated in tumor progression and considered as a tumor suppressor. Aim of the study is to investigate the role of SPARCL1 in the regulation of tumor biology. SPARCL1 expression in human cervical cells was determined through western blot and RT-PCR. The effects of SPARCL1 overexpression on cell proliferation, migration and invasion were evaluated through CCK8 assay, colony formation assay, Wound healing assay and Transwell assay, respectively. The gain function of Secreted phosphor protein 1 (SPP1) was also evaluated in these cell functions. We observed that SPARCL1 expression at protein levels and transcription levels was lower in HeLa cells than that in Ect1/E6E7 cells. When SPARCL1 was overexpressed in HeLa cells, cell proliferation, migration and invasion were greatly repressed. Additionally, SPARCL1 overexpression markedly downregulated SPP1 expression at transcription levels. Mechanistical study revealed that SPP1 overexpression could greatly counteract the effects of SPARCL1 overexpression on the aforementioned cell processes and inhibit the phosphorylation of focal adhesion kinase (FAK) and extracellular regulated protein kinases (ERK). Our findings indicated that HeLa cells overexpressing SPARCL1 showed weaker abilities of proliferation, migration and invasion, and its effects could be neutralized by SPP1 overexpression possibly via FAK/ERK pathway. The relationship of SPARCL1 and SPP1 could help us to further understand the pathogenesis of cervical cancer and SPARCL1/SPP1 could be beneficial therapeutic targets in cervical cancer.