New Review Shows Progranulin’s Critical Role in Cancer

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by the Sbarro Health Research Organization (SHRO)

Structure, processing and trade of progranulin. The growth factor progranulin is a modular protein containing seven and a half non-identical cysteine-rich tandem repeats known as granulin domains. Progranulin can be processed by several proteases into individual granulin modules. Progranulin is released into the extracellular environment by regulated exocytosis. Extracellular progranulin can be internalized and sorted in lysosomes in a sortilin- or prosaposin-dependent manner, but can also enter the lysosomes via the secretory pathway. In lysosomes, progranulin is processed into granulins by cathepsin L. Whether progranulin could be endocytosed independently of sortilin and prosaposin by binding to other receptors has not yet been fully clarified. ER: endoplasmic reticulum. TGN: Trans-Golgi Network. Credit: Cancer (2023). DOI: 10.3390/Krebs15061706

A recent review published in the journal Cancers highlights the important role of the growth factor progranulin in the development and progression of cancer.

Progranulin has been found to play a protumorogenic role in cancer by promoting proliferation, migration, invasiveness, anchorage-independent growth, and resistance to chemotherapy of cancer cells. In addition, progranulin regulates the tumor microenvironment, affects the function of cancer-associated fibroblasts, and modulates tumor immune surveillance. However, the molecular mechanisms of the oncogenic function of progranulin are not yet fully understood.

This review was recently published by researchers affiliated with the Sbarro Health Research Organization (SHRO) and the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University, led by Founder and Director Antonio Giordano, MD Ph.D.

The Progranulin Oncogenic Network in Solid Tumors paper was written by Elisa Ventura, Ph.D, and Andrea Morrione, Ph.D, Temple University, with co-authors including Drs. Giordano and others at Thomas Jefferson University and Universities in, Milan and Catania.

The authors provide a detailed overview of the current state of knowledge on the function of progranulin in tumors, with a focus on its molecular mechanisms of action and regulation. Understanding the details of progranulin function may lead to the identification of new targets for cancer therapy.

This work covers the current literature supporting the notion that the action of progranulin is critical to the initiation and progression of mesothelioma. Further investigation of progranulin could lead to the development of new therapeutic strategies targeting progranulin in mesothelioma and other cancers.

“This paper is significant because it highlights the critical role of progranulin in carcinogenesis and provides valuable insight into the possibility of progranulin as a novel target for cancer therapy,” says Giordano. With further research, progranulin could potentially be used as a diagnostic and prognostic marker for various types of cancer.

For more information: Elisa Ventura et al., Progranulin Oncogenic Network in Solid Tumors, Cancers (2023). DOI: 10.3390/Krebs15061706

Provided by the Sbarro Health Research Organization (SHRO)