Dissecting IL-2 Signaling Pathway in Non-Small-Cell Lung Cancer Stem Cells

Background and Aim: Lung cancer is one of the most common cancersworldwide. Cancer stem cells (CSC) are known to initiate lung cancer.CSC are capable to differentiate into many cells and driving tumor growthby attenuating immune surveillance through secretion or expressionof immune-suppressive factors or by the recruitment of accessory cellsthat locally suppress the immune response. Therefore, recognizing thesignaling pathways by which CSC manipulates the immune system toescape recognition is of utmost importance.Methods: Cancer stem cells were isolated from normal lung epithelialcells and lung cancer cell lines (A549 and NCI-H 2170, respectively).Using Affymetrix microarray, the transcriptome of the normal andcancerous stem cells was compared in GEO2R software and the resultswere analyzed in Reactome software. Eventually, signaling pathwaysending in IL-2 in stem cells were evaluated.Results: To activate interleukin 2 cancer stem cells, beta-interleukin 2receptor binds to JAK1 and IL-2RG binds to JAK3. The IL-2 alpha receptoris attached to IL-2 and these two are linked to IL-2 beta receptor and theIL-2 beta receptor binds to the gamma subunit of the IL-2 alpha receptor.The complex JAK1 and JAK3 phosphorylate IL2R and JAK1, Y392,Y338, Y510 phosphorylate IL-2 beta receptor. Y338 phosphorylationof Interleukin-2 beta receptor enables SHC and Y392, Y338, or Y510phosphorylation of interleukin-2 beta receptor enables STAT. SH1attached to the interleukin 2 and STAT5 receptors are phosphorylated.Phosphorylated STAT5 dimerizes and goes to the nucleus. SYK is boundto Interleukin 2 beta receptor and is a substrate for JAK1. PTK2B isconnected to JAK3 and is phosphorylated.Conclusion: CSC can affect other cells through signaling pathwaysleading to the production of interleukins. This effect can be one of theescaping mechanisms from the immune system. Currently, Interleukin 2is used to treat cancers, but the same interleukin can also convert adult Tcell into Treg cells. Therefore, recognizing the signaling pathway leadingto the production of interleukin 2 in cancer stem cells can provide aprecise vision for new therapeutic processes.

کلیدواژه ها:

Cancer stem cell ، Interleukin 2 ، Signaling ، Immune system