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. 2019 Sep;234(9):15581-15593.
doi: 10.1002/jcp.28205. Epub 2019 Jan 31.

SPARC promotes the proliferation and metastasis of oral squamous cell carcinoma by PI3K/AKT/PDGFB/PDGFRβ axis

Yue Jing  1 , Yue Jin  2 , Yujia Wang  2 , Sheng Chen  2 , Xiaoxin Zhang  1 , Yuxian Song  1 , Zhiyong Wang  2 , Yumei Pu  2 , Yanhong Ni  1 , Qingang Hu  2
Affiliations

SPARC promotes the proliferation and metastasis of oral squamous cell carcinoma by PI3K/AKT/PDGFB/PDGFRβ axis

Yue Jing et al. J Cell Physiol. 2019 Sep.

Abstract

Oral squamous cell carcinoma (OSCC) is a highly lethal cancer in the world, and the prognosis of OSCC is poor with a 60% 5-year survival rate in recent decades. Here, we introduced a novel secretory and acid glycoprotein with cysteine rich (secreted protein acidic and rich in cysteine, SPARC), which is correlated with the worst pattern of invasion (WPOI) and prognosis of OSCC. SPARC expression levels were measured in OSCC tissues and normal tissues using quantitative polymerase chain reaction and immunohistochemistry. The influence of SPARC on cell proliferation was examined by cell counting kit-8, colony formation, and Edu tests. Then, the effect of SPARC on the metastasis of OSCC cells was detected by wound healing and transwell migration assays. Next, the biologic characteristics of SPARC shared by STRING were analyzed. Furthermore, the underlying mechanisms were confirmed by western blot analysis. SPARC revealed higher expression in OSCC tissues than nontumor tissues. Higher SPARC expression was correlated with poorer tumor differentiation, poorer WPOI pattern, and significantly and shorter overall survival. Knockdown SPARC significantly restrained OSCC cell growth, migration, and invasion. In addition, bioinformatics analysis found SPARC had a coexpression network with the platelet-derived growth factor-B (PDGFB) and PI3K/AKT signaling pathways with minimal false discovery rate. Furthermore, SPARC promotes OSCC cells metastasis by regulating the expressions of PDGFB, PDGFRβ, p-PDGFRβ , and the PI3K/AKT pathway. Higher SPARC expression was positively correlated with poor WPOI and differentiation in OSCC. SPARC activates the PI3K/AKT/PDGFB/PDGFRβ axis to promote proliferation and metastasis by OSCC cell lines. Therefore, SPARC may be a potential therapeutic target for patients with OSCC.

Keywords: SPARC; WPOI; migration and invasion; oral squamous cell carcinoma.

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References

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