Table 2.

Nucleocytoplasmic mechanisms of aggressive melanoma and thyroid cancer.

Signal Transducer	Translocation Effects	Oncogenic Role	Specific Cancer	References
FOXO1, FOXO3a, FOXO4, FOXO6	Cytoplasmic mislocalization promoted by Akt. Nuclear localization of Akt in thyroid cells increases oncogenic expression, high metastatic invasion in lymph nodes and tumor aggression	Activate transcription of genes that triggers cellular proliferative, cell cycle, differentiation, and cell death.	Melanoma, thyroid cancer	Kau et al., 2004; Tang et al., 1999, Takaishi et al., 1999; Nakamura et al., 2000
Claudin-1	Translocation from nucleus to cytoplasm in melanoma cells and increased cytoplasmic expression in a PKC-dependent manner but altered migration by PKA Phosphorylation.	Increased expression, invasiveness in melanoma hence a marker of progression	Melanoma	French et al., 2009; Leotlela et al., 2007
B-catenin	Nuclear expression	Tumor suppressor role in primary and secondary tumors	Melanoma, thyroid cancer	Chien et al., 2009
Cyclin D1	Cytoplasmic claudin-1 is highly expressed with more aggression and increased invasiveness in melanoma unlike benign nuclear claudin-1	Accumulation of cells in the G1 phase of cell cycle.	Melanoma	French et al., 2009; Leotlela et al., 2007
CDKN1B (p27)	Phosphorylated by Akt and exported from nucleus to cytoplasm. Cytoplasmic expression is associated with poor 5-year survival in metastatic melanoma	A cell-cycle inhibitor, blocks cell cycle in the G0/G1 differentiation signals or cellular stress —cell cycle, activation of PI3K and MEK-dependent kinases	Thyroid, melanoma	Kau et al., 2004
p53	Mutation, post-translational modification, or cytoplasmic mislocalization	Acts as a tumor suppressor and trigger cell cycle arrest, apoptosis, senescence, DNA repair, DNA damage and change the metabolism depending on physiological conditions. Also, known as Guardian of the genome.	Melanoma	Fabbro & Henderson, 2003; Webster et al., 2019
NF-kB	Nuclear import of NF-κB leads to increased target gene expression leading to promotion of tumorigenesis and resistance to anticancer therapies	Activate NF-kB signaling and induce apoptosis of cancer cells.	Thyroid cancer	Kau et al., 2004
Muc 1/EGFR	MUC1 confers survival advantage in melanoma, overexpression of EGFR and nuclear mislocalization is associated with aggressiveness	Induce oncogene expression through interaction with β-catenin and EGFR.	Melanoma and thyroid cancer	Zhao et al., 2014; Patel et al., 2005; Ward et al., 2007