Transforming growth factor‐β pathway is one of the most commonly altered cellular signaling pathways in human cancer, which plays a crucial role as both a tumor suppressor in early stage carcinogenesis and pro‐metastatic factor in advanced stages of tumors.32,33 TGFβ isoforms exert their cellular effects by binding to the TGF‐β type II receptor (TGFBR2), and this binding facilitates activation of TGFBR1 kinase, which leads to the activation of Smad and non‐Smad pathway, thereby regulating the transcription of specific genes.34,35 The non‐Smad pathway acts through the intracellular MAPK signaling cascades (ERK1/2, JNK1/2/3 and p38MAPK being the 3 major branches of the stress‐induced activation of the MAPK pathway).36 MAPK cellular signaling pathway, frequently activated in the thyroid carcinogenesis, transmits growth signals from the plasma membrane to the nucleus and plays a central part in promoting cancer cell proliferation and survival.37,38,39 Shen et al report that miRNA‐106a directly targeting RARB influence the viability, apoptosis, differentiation of PTC, and alter the iodine uptake function by regulating MAPK pathway.40 Here, we unravel for the first time that SLC35F2 exerts its oncogenic effect on PTC progression mainly through the MAPK pathway, with dependence on the induction and activation of TGFBR‐1 and ASK‐1.

 Transforming growth factor‐β pathway is one of the most commonly altered cellular signaling pathways in human cancer, which plays a crucial role as both a tumor suppressor in early stage carcinogenesis and pro‐metastatic factor in advanced stages of tumors.32,33 TGFβ isoforms exert their cellular effects by binding to the TGF‐β type II receptor (TGFBR2), and this binding facilitates activation of TGFBR1 kinase, which leads to the activation of Smad and non‐Smad pathway, thereby regulating the transcription of specific genes.34,35 The non‐Smad pathway acts through the intracellular MAPK signaling cascades (ERK1/2, JNK1/2/3 and p38MAPK being the 3 major branches of the stress‐induced activation of the MAPK pathway).36 MAPK cellular signaling pathway, frequently activated in the thyroid carcinogenesis, transmits growth signals from the plasma membrane to the nucleus and plays a central part in promoting cancer cell proliferation and survival.37,38,39 Shen et al report that miRNA‐106a directly targeting RARB influence the viability, apoptosis, differentiation of PTC, and alter the iodine uptake function by regulating MAPK pathway.40 Here, we unravel for the first time that SLC35F2 exerts its oncogenic effect on PTC progression mainly through the MAPK pathway, with dependence on the induction and activation of TGFBR‐1 and ASK‐1.

 (C) CD95 induces activation of the MAPK pathway in a DD-independent manner by stimulating EGFR.

 (B) CD95 induces caspase-dependent activation of the MAPK pathway.

 Transforming growth factor‐β pathway is one of the most commonly altered cellular signaling pathways in human cancer, which plays a crucial role as both a tumor suppressor in early stage carcinogenesis and pro‐metastatic factor in advanced stages of tumors.32,33 TGFβ isoforms exert their cellular effects by binding to the TGF‐β type II receptor (TGFBR2), and this binding facilitates activation of TGFBR1 kinase, which leads to the activation of Smad and non‐Smad pathway, thereby regulating the transcription of specific genes.34,35 The non‐Smad pathway acts through the intracellular MAPK signaling cascades (ERK1/2, JNK1/2/3 and p38MAPK being the 3 major branches of the stress‐induced activation of the MAPK pathway).36 MAPK cellular signaling pathway, frequently activated in the thyroid carcinogenesis, transmits growth signals from the plasma membrane to the nucleus and plays a central part in promoting cancer cell proliferation and survival.37,38,39 Shen et al report that miRNA‐106a directly targeting RARB influence the viability, apoptosis, differentiation of PTC, and alter the iodine uptake function by regulating MAPK pathway.40 Here, we unravel for the first time that SLC35F2 exerts its oncogenic effect on PTC progression mainly through the MAPK pathway, with dependence on the induction and activation of TGFBR‐1 and ASK‐1.

 (B) CD95 induces caspase-dependent activation of the MAPK pathway.

 (A) CD95 induces DD-mediated caspase-independent activation of the MAPK pathway.

 Frequent activation of the MAPK pathway in MCL is well characterized and occurs as a consequence of FAK (protein tyrosine kinase 2) and CXCR4 upregulation, which are directly influenced by SOX11, a key diagnostic antigen in MCL., Upregulation of FAK leads to activation of ERK1/2, NF-κB, and AKT, which is often associated with treatment resistance in MCL., , MAPK pathway activation contributes to several cellular functions including apoptosis, migration, invasion, proliferation, and angiogenesis and has been associated with stem-like properties in MCL., Both p-ERK and p38, part of MAPK signaling, are associated with inferior outcomes in MCL.

 Frequent activation of the MAPK pathway in MCL is well characterized and occurs as a consequence of FAK (protein tyrosine kinase 2) and CXCR4 upregulation, which are directly influenced by SOX11, a key diagnostic antigen in MCL., Upregulation of FAK leads to activation of ERK1/2, NF-κB, and AKT, which is often associated with treatment resistance in MCL., , MAPK pathway activation contributes to several cellular functions including apoptosis, migration, invasion, proliferation, and angiogenesis and has been associated with stem-like properties in MCL., Both p-ERK and p38, part of MAPK signaling, are associated with inferior outcomes in MCL.

 SHP2 positively regulates (ERK)/MAPK signal transduction and downregulation of the (ERK)/MAPK pathway, due to the disruption of Shp2, leads to the formation of skeletal abnormalities and skull defects in mice , .We show that at 5dpf, pERK levels are downregulated in ptpn11a-/-ptpn11b-/- embryos, which is consistent with an essential role for Shp2 in Erk/MAPK signaling upstream of craniofacial development.