FAM83F Protein Implicated in Papillary Thyroid Cancer and Drug Resistance

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The FAM83F protein contributes to papillary thyroid cancer cell viability and doxorubicin resistance, according to a study presented at the 85th Annual Meeting of the ATA.

The FAM83F protein contributes to papillary thyroid cancer (PTC) cell viability and doxorubicin resistance, according to authors of a preclinical lab study reported at the 15th International Thyroid Congress (ITC) and 85th Annual Meeting of the American Thyroid Association (ATA) this week in Lake Buena Vista, Florida.

FAM83F is overexpressed in human PTC, and exerts a pro-oncogenic role that involves the reduction of thyroid cell differentiation and activation of stem cell genes to increase cell viability, migration, and resistance to doxorubicin,” reported lead study author Cesar Seigi Fuziwara, PhD, of the department of cell and developmental biology at the University of São Paulo, São Paulo, Brazil.

Molecular profiling has revealed that PTCs frequently harbor genetic mutations in the mitogen-activated protein kinases (MAPK) signaling pathway, such as altered RET, RAS, and BRAF genes, Dr. Fuziwara noted.

Just how these genetic alterations contribute to aggressive tumor behavior is incompletely understood, but there is reason to suspect that FAM83F proteins might play a role in PTC aggressiveness, including treatment resistance, Dr. Fuziwara said. Expression of FAM83 genes is elevated in treatment-refractory breast and lung cancer, he noted.

“Previously, our group has identified in the Human Genome Cancer Project (FAPESP/LICR) FAM83F gene (previously, LOC113828) located at chromosome 22. The family of FAM83 is composed by eight members, from FAM83A to FAM83H,” said Dr. Fuziwara. “Interestingly, goiter displays nuclear staining of FAM83F, while PTC from BRAF-transgenic mice (Tg-BRAF) exhibits high expression of FAM83F.”

To study the role of FAM83F in PTC, Dr. Fuziwara and his coauthors used immunohistochemistry and protein levels to measure FAM83F gene expression in human thyroid tumors and Tg-BRAF mice. They then experimentally overexpressed FAM83F in vitro to analyze human thyroid cell viability, migration, and doxorubicin resistance.

FAM83F was overexpressed in PTC. Experimental overexpression increased cell viability, migration, and doxorubicin resistance, and cell “stemness” markers (Lin28b and Hmga2 expression) in thyroid cells, and reduced cell differentiation, he reported.

FAM83F overexpression increases resistance to doxorubicin,” concluded Dr. Fuziwara.

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