International Journal of Cell Biology / 2013 / Article / Tab 1

Review Article

Regulation of the Ras-MAPK and PI3K-mTOR Signalling Pathways by Alternative Splicing in Cancer

Table 1

Alternative splicing of Ras-MAPK and PI3K-mTOR signaling components.

Signalling componentGene nameSplicing isoform activityType of cancerReference number

RTKEGFRConstitutively active receptor/soluble decoy isoform, enhanced signalling, survival, and tumorigenicity. Glioblastoma, lung[28, 4749, 51, 5658]
RTKRONConstitutively active receptor, enhanced signalling, invasion, and motility.Glioblastoma, colon, breast, and gastric[34, 35]
RTKMETConstitutively active receptor/soluble decoy isoform, enhanced/reduced signalling, invasion, and motility.Ovarian, lung, and HCC[38, 39]
RTKFGFRInduction of EMT, invasion, and motility.Prostate, pancreatic, and breast[28, 29, 36, 61]
RTKINSRDifferential ligand binding (IGF-II) and oncogenic activity.HCC, thyroid, and ovarian[31, 37]
RTKVEGFRSoluble decoy isoform, enhanced/reduced angiogenesis, and survival.Lung, breast[28, 32]

Cytosolic kinaseFynEnhanced/reduced kinase activity, survival of epithelial cells.Unknown[43]
Cytosolic kinasemTORConstitutively active kinase, oncogenic activity.HCC[75]
Cytosolic kinaseS6K1Tumor suppressor/oncogenic isoforms, activates/inhibits mTORC1.Breast, lung[14, 78]
Cytosolic kinaseA-RafEnhanced/reduced binding to Ras and activation of the MAPK pathway.HCC, head, and neck[45, 46]
Cytosolic kinaseB-RafEnhanced/reduced kinase activity, activation of the MAPK pathway, and resistance to BRAF kinase inhibitors.Colon, melanoma[20, 21, 40]
Cytosolic kinaseMEK1Alternative pathway with a different substrate.Unknown[66, 67]
Cytosolic kinaseERK1Alternative pathway with different substrates.Unknown[66, 67]
Cytosolic kinaseMKNK2Oncogenic isoform that enhances eIF4E phosphorylation and a tumor-suppressive isoform.Lung, breast, colon, and pancreas[14, 68]

Phospholipid phosphatasePTENActive/inactive tumor suppressor.Unknown[71]
Phospholipid kinasePI3KConstitutively active kinase, enhanced downstream signalling.Unknown[69, 70]

Small GTPaseRasEnhanced/reduced binding to Raf and Rin and activation of the MAPK pathway.Unknown[32, 44]
GTPase activator (GAP)TSC2Inactivation of a tumor suppressor.Tuberous sclerosis[7274]

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