Desulfation of cell surface HSPG is an effective strategy for the treatment of gallbladder carcinoma.

Cell surface heparan sulfate proteoglycan (HSPG) is a group of critical glycoproteins that mediates signal transduction. Sulfated HSPG can mediate the activation of a variety of cell growth factor signal pathway to promote the progression of gallbladder carcinoma (GBC). This study analyzed 527 clinical GBC specimens and confirmed that the HSPG sulfation level was significantly higher in GBC tissues than in gallbladder mucosa (GBM) tissues. The high HSPG sulfation level was closely associated with poor differentiation, local metastasis, and advanced clinical stage of GBC; it was also associated with the shortening of disease-free survival (DFS) and overall survival (OS) and influenced the outcome of chemotherapy or radio-chemotherapy in patients with GBC recurrence. Inhibition of HSPG sulfation on the GBC cell surface using human sulfatase 1 (hSulf-1) significantly reduced the phosphorylation levels of growth factor receptors and signaling protein kinases in GBC cells, decreased cell responses to growth factors, and inhibited cell proliferation and migration abilities. In a nude mouse model with GBC xenografts, we observed that the xenograft tumor growth was suppressed and the phosphorylation levels of signaling proteins were downregulated, together with decreased expression of Ki67 and reduced sensitivity to bFGF (basic fibroblast growth factor) induction after inhibition of HSPG sulfation. Our study demonstrated that a high HSPG sulfation endows GBC with high malignant biological behaviors and a poor prognosis. Desulfation of cell surface HSPG can inhibit the kinase activities of a variety of signaling proteins, hinder the cell response to growth factors, and effectively inhibit the malignant biological behaviors of GBC cells.

Yi B ，Qiu Y ，Ji W ，Wei M ，Liu C ，Peng Z ，Zhang Y ，Quan Z ，Tang Z ，Su C ... -  《-》

Protein phosphatase PHLPP induces cell apoptosis and exerts anticancer activity by inhibiting Survivin phosphorylation and nuclear export in gallbladder cancer.

Qiu Y ，Li X ，Yi B ，Zheng J ，Peng Z ，Zhang Z ，Wu M ，Shen F ，Su C ... -  《-》

SNORA74B gene silencing inhibits gallbladder cancer cells by inducing PHLPP and suppressing Akt/mTOR signaling.

Qin Y ，Meng L ，Fu Y ，Quan Z ，Ma M ，Weng M ，Zhang Z ，Gao C ，Shi X ，Han K ... -  《-》

SPOCK1 as a potential cancer prognostic marker promotes the proliferation and metastasis of gallbladder cancer cells by activating the PI3K/AKT pathway.

Shu YJ ，Weng H ，Ye YY ，Hu YP ，Bao RF ，Cao Y ，Wang XA ，Zhang F ，Xiang SS ，Li HF ，Wu XS ，Li ML ，Jiang L ，Lu W ，Han BS ，Jie ZG ，Liu YB ... -  《Molecular Cancer》

Skp2-RNAi suppresses proliferation and migration of gallbladder carcinoma cells by enhancing p27 expression.

Zhang B ，Ji LH ，Liu W ，Zhao G ，Wu ZY ... -  《-》