Secreted protein acidic and rich in cysteine (SPARC) plays a key role in the progression of cholangiocarcinoma (CCA) via the phosphoinositide 3-kinase-AKT serine/threonine kinase (PI3K-AKT) signaling pathway, a new study published in Tissue and Cell found.

This finding suggests that targeting SPARC may be a promising avenue to improve outcomes in patients with CCA. Although the molecular mechanism of the development and progression of CCA is still not well understood, research has shown that SPARC may be involved.

In the present study, a team of researchers from China investigated the functional role of SPARC in CCA progression. They first analyzed the expression of SPARC in CCA cells and tissues and saw that this expression was significantly increased. 

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When they knocked down the expression of SPARC using RNA interference, the proliferation of CCA cells was significantly slowed down. Lowering the expression of SPARC also inhibited the migration and invasion of CCA cells by blocking epithelial to mesenchymal transition.

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In a reverse experiment, the researchers showed that overexpressing SPARC in a human CCA cell line increased their proliferation, migration, and invasion. Thus, the researchers found that this happened through the activation of the PI3K-AKT signaling.

“SPARC knockdown significantly suppressed the phosphorylation of PI3K and AKT,” they wrote. Moreover, silencing SPARC reduced the activity, and overexpressing it increased the activity of PI3K.

They concluded that SPARC activates the PI3K-AKT signaling in CCA cells and promotes epithelial to mesenchymal transition resulting in the malignant phenotype observed in vitro. “Our data is anticipated to provide insight into SPARC as a new therapeutic target for CCA,” they wrote.

SPARC is a member of the matricellular protein family. It is involved in the regulation of many different cellular processes such as cell communication, proliferation, and metastasis, as well as tissue remodeling. Research has shown that its expression is abnormal in many human tumors.


Deng S, Zhang L, Li J, Jin Y, Wang J. Activation of the PI3K-AKT signaling pathway by SPARC contributes to the malignant phenotype of cholangiocarcinoma cells. Tissue Cell. Published online February 10, 2022. doi:10.1016/j.tice.2022.101756