Solute carrier family 35 member F2 is indispensable for papillary thyroid carcinoma progression through activation of transforming growth factor‐β type I receptor/apoptosis signal‐regulating kinase 1/mitogen‐activated protein kinase signaling axis

Abstract

Solute carrier family members control essential physiological functions and are tightly linked to human diseases. Solute carrier family 35 member F2 (SLC35F2) is aberrantly activated in several malignancies. However, the biological function and molecular mechanism of SLC35F2 in papillary thyroid carcinoma (PTC) are yet to be fully explored. Here, we showed that SLC35F2 was prominently upregulated in PTC tissues at both protein and mRNA expression level compared with matched adjacent normal tissues. Besides, the high expression of SLC35F2 was significantly associated with lymph node metastasis in patients with PTC. CRISPR/Cas9‐mediated knockout of SLC35F2 attenuated the tumorigenic properties of PTC, including cell proliferation, migration and invasion and induced G1 phase arrest. In contrast, ectopic expression of SLC35F2 brought about aggressive malignant phenotypes of PTC cells. Moreover, SLC35F2 expedited the proliferation and migration of PTC cells by targeting transforming growth factor‐β type I receptor (TGFBR1) and phosphorylation of apoptosis signal‐regulating kinase 1 (p‐ASK‐1), thereby activating the mitogen‐activated protein kinase signaling pathway. The malignant behaviors induced by overexpression of SLC35F2 could be abrogated by silencing of TGFBR1 using a specific inhibitor. We conducted the first study on SLC35F2 in thyroid cancer with the aim of elucidating the functional significance and molecular mechanism of SLC35F2. Our findings suggest that SLC35F2 exerts its oncogenic effect on PTC progression through the mitogen‐activated protein kinase pathway, with dependence on activation of TGFBR‐1 and apoptosis signal‐regulating kinase 1.

Expression analysis and functional identification of several genes related to diapause in Bombyx mori

“…It may be involved in transmembrane transport of glucose, amino acids and other substances (Ashikov et al., ; Kashiwaya et al., ). The downregulation of BGIBMGA003835 and BGIBMGA012335 that we observed in PNDD can be expected to equate to upregulation in diapause meaning that the manufacture and storage of glycogen is increased in diapauses, potentially influencing several signaling pathways such as the mitogen‐activated protein kinase (MAPK) pathway (Fujiwara & Shiomi, ; He et al., ). The gene product of BGIBMGA002426 is mannosyl‐oligosaccharide α‐1,2‐mannosidase, which is involved in the procession of protein or peptide in endoplasmic reticulum (Wilson, ).…”

lncRNA SNHG3 acts as a novel Tumor Suppressor and regulates Tumor Proliferation and Metastasis via AKT/mTOR/ERK pathway in Papillary Thyroid Carcinoma

“…Apart from the AKT/mTOR pathway, MAPK/ERK pathway is also an important intracellular signaling pathway through a p53-dependent regulation of cell cycle [32]. MAPK signaling pathway transmits growth signals from the cell membrane to the cell nucleus and plays a crucial role in promoting PTC cell proliferation and survival [33].…”

The pathognomonic FOXL2 C134W mutation alters DNA binding specificity

“…Strikingly, all four genes identified are highly relevant to cancer biology ( Table 1). CHRNA9 has been previously identified as highly expressed in breast cancer 41 ; S1PR1 is a G-protein coupled receptor involved in the cytokine signaling in the immune system, and is known to be up-regulated in ovarian cancer tissues and cell lines 42 ; SLC35F2 is a potential oncogene highly expressed in non-small-cell lung carcinoma 43 , indispensable for papillary thyroid carcinoma progression 44 , and regulated by androgen receptor axis signaling in prostate cancer 45 ; ATP5E is known to be down regulated in papillary thyroid cancer 46 . These findings prompted us to examine whether those genes were also expressed in primary AGCTs 7 .…”