The expression of the p62 protein is significantly upregulated in intrahepatic cholangiocarcinoma (ICC) compared to healthy tissue, according to a new study under review to be published in the journal Cancer Cell International.
Moreover, the expression of the protein is positively correlated with lymph node metastasis and poor prognosis.
“These data provide new evidence and [a] feasible mechanism that abundant p62 expression promotes ICC progression, suggesting a promising therapeutic target for anti-metastatic strategies in ICC patients,“ the researchers wrote.
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p62 is a cargo protein of the autophagosome. When other proteins bind to it, it targets them for selective autophagy. It also regulates multiple signaling pathways and participates in the initiation and spread of tumors.
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A team of researchers from Fudan University Zhongshan Hospital in China investigated the role of p62 in ICC progression.
First, they analyzed the expression of the protein in ICC tissues using Western blotting and immunohistochemistry and compared this to healthy tissues. Then, they conducted loss of function experiments to identify the role of p62 in the progression of the disease. Finally, they evaluated mitochondrial function and mitophagy, or the selective degradation of mitochondria by autophagy, in ICC tissue.
The loss of function experiments showed that p62 promoted the proliferation, migration, and invasiveness of ICC cells in vitro. They also showed that it induced lung metastasis in a xenograft mouse model.
The high expression of p62, the researchers found, induced epithelial-mesenchymal transition by upregulating the expression of some proteins such as Snail1 and Vimentin and downregulating the expression of others such as E-Cadherin.
The assessment of mitochondrial function and mitophagy led the researchers to conclude that p62 may play a crucial role in maintaining mitochondrial function in ICC tissue, thereby promoting tumor progression.
Reference
Chen J, Gao Z, Li X, et al. SQSTM1/p62 in intrahepatic cholangiocarcinoma promotes tumor progression via epithelial-mesenchymal transition and mitochondrial function maintenance. Research Square. Preprint posted online October 18, 2021. doi:10.21203/rs.3.rs-964992/v1
