![]() ![]() Knocking down ZIP10 in mannose-insensitive cells significantly inhibited in vitro and in vivo growth of these cells by decreasing intracellular Zn ²⁺ concentration and enzyme activity of PMI. Further studies found that the expression of zinc transport protein ZIP10, which transport Zn ²⁺ from extracellular area into cells, was negatively related to the response of thyroid cancer cells to mannose. Besides, our data showed that zinc ion (Zn ²⁺ ) chelator TPEN clearly increased the response of mannose-insensitive cells to mannose by inhibiting enzyme activity of PMI, while Zn ²⁺ supplement could effectively reverse this effect. Our data demonstrated that mannose selectively suppressed the growth of thyroid cancer cells, and found that enzyme activity of PMI rather than its protein expression was negatively associated with the response of thyroid cancer cells to mannose. The underlying mechanism of mannose selectively killing thyroid cancer cells was clarified by a series of molecular and biochemical experiments. ![]() Meanwhile, mouse models of subcutaneous xenograft and primary papillary thyroid cancer were established to determine in vivo anti-tumor activity of mannose. MTT, colony formation and flow cytometry assays were performed to determine the response of thyroid cancer cells to mannose. However, its function in thyroid cancer still remains elusive. Mannose, a natural hexose existing in daily food, has been demonstrated to preferentially inhibit the progression of tumors with low expression of phosphate mannose isomerase (PMI). Our results establish a role of ZIP10 in cell survival during early B-cell development, and underscore the importance of Zn homeostasis in immune system maintenance. Moreover, we found that ZIP10 expression was regulated by JAK-STAT pathways, and its expression was correlated with STAT activation in human B-cell lymphoma, indicating that the JAK-STAT-ZIP10-Zn signaling axis influences the B-cell homeostasis. Collectively, these findings indicated that ZIP10-mediated Zn homeostasis is essential for early B-cell survival. Similarly, the depletion of intracellular Zn by a chemical chelator resulted in spontaneous caspase activation leading to cell death. Genetic ablation of Zip10 in early B-cell stages resulted in significant reductions in B-cell populations, and the inducible deletion of Zip10 in pro-B cells increased the caspase activity in parallel with a decrease in intracellular Zn levels. Here we investigated ZIP10, a Zn transporter expressed in the early B-cell developmental process. ![]() The immune system is influenced by the vital zinc (Zn) status, and Zn deficiency triggers lymphopenia however, the mechanisms underlying Zn-mediated lymphocyte maintenance remain elusive. ![]()
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