Abstract
Activation of plasminogen on the cell surface initiates a cascade of protease activity with important implications for several physiological and pathological events. In particular, components of the plasminogen system participate in tumor growth, invasion and metastasis. Plasminogen receptors are in fact expressed on the cell surface of most tumors, and their expression frequently correlates with cancer diagnosis, survival and prognosis. Notably, they can trigger multiple specific immune responses in cancer patients, highlighting their role as tumor-associated antigens. In this review, three of the most characterized plasminogen receptors involved in tumorigenesis, namely Annexin 2 (ANX2), Cytokeratin 8 (CK8) and alpha-Enolase (ENOA), are analyzed to ascertain an overall view of their role in the most common cancers. This analysis emphasizes the possibility of delineating new personalized therapeutic strategies to counteract tumor growth and metastasis by targeting plasminogen receptors, as well as their potential application as cancer predictors.
Highlights
The plasminogen system is involved in tumor growth, invasion and metastasis [1,2,3,4,5]
This review aims to analyze the plasminogen receptors Annexin 2 (ANX2), Cytokeratin 8 (CK8) and alpha-Enolase (ENOA) in the most common tumors and to correlate their expression with specific immune responses and/or clinical outcomes
The effect of CK8 over-expression on survival remains controversial as in non-small cell lung carcinomas (NSCLC), increasing serum levels of CK8 were significantly associated with tumor progression and lower patient survival [126,142], whereas breast cancer patients with low expression of CK8 and high expression of Human Epidermal Growth Factor Receptor 2 (HER2) have a higher risk of recurrence and death within 5 years (Table 2) [131]
Summary
The plasminogen system is involved in tumor growth, invasion and metastasis [1,2,3,4,5]. The effect of CK8 over-expression on survival remains controversial as in non-small cell lung carcinomas (NSCLC), increasing serum levels of CK8 were significantly associated with tumor progression and lower patient survival [126,142], whereas breast cancer patients with low expression of CK8 and high expression of Human Epidermal Growth Factor Receptor 2 (HER2) have a higher risk of recurrence and death within 5 years (Table 2) [131]. ANX2, ENOA and CK8 all interact with the actin cytoskeleton and such an association could promote the migration of tumor cells independently from plasminogen-binding [29] These three receptors are present on the surface of the majority of human neoplasms, and in some cases, such as breast and colon, they are expressed altogether. The ENOA-DNA vaccine significantly decreased suppressor cells such as myeloid-derived suppressor cells and regulatory T cells [186]
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