Cancer development, chemoresistance, epithelial to mesenchymal transition and stem cells: A snapshot of IL-6 mediated involvement. Issue 1 (28th May 2016)

• Record Type: Journal Article
• Authors: Bharti, Rashmi; Dey, Goutam; Mandal, Mahitosh
• Is Part Of: Cancer letters. Volume 375:Issue 1(2016)
• Page Start: 51
• Page End: 61
• Publication Date: 2016-05-28
• Subjects: Cytokine -- IL-6 -- Cancer stem cell -- Chemoresistance and EMT; MAPK mitogen-activated protein kinases -- STAT3 signal transducer and activator of transcription 3 -- gp130 glycoprotein 130 -- C/EBP CCAAT/enhancer-binding protein -- JAK Janus kinase -- PI3K phosphoinositide 3-kinase -- Bcl-2 B-cell lymphoma 2 -- BAX BCL2-associated X protein -- NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells -- LPA lysophosphatidic acid -- LPAR2 lysophosphatidic acid receptor2 -- EZH2 enhancer of zeste homolog 2 -- AP-1 activator protein 1 -- Fra-1 Fos-related antigen 1 -- HP1 heterochromatin Protein 1 -- VEGF vascular endothelial growth factor -- TIMP-1 tissue inhibitor of metalloproteinase 1 -- CCL2 chemokine (C-C motif) ligand 2 -- MCP-1 monocyte Chemoattractant Protein-1 -- HSF 1 heat shock transcription factor 1 -- JNKs c-Jun N-terminal kinases -- Rho A Ras homolog gene family, member A -- ROCK Rho-associated protein kinase -- ERK extracellular signal regulated kinases -- OCT-4 octamer binding transcription factor-4 -- TGF-β transforming growth factor beta -- FGF fibroblast growth factors -- MMP matrix metalloproteinases -- ZEB1 zinc finger E-box-binding homeobox 1 -- MDR1 multidrug resistance protein 1 -- MRP1 multidrug resistance-associated protein1 -- PTEN phosphatase and tensin homolog -- XIAP X-linked inhibitor of apoptosis protein -- HNF-4α hepatocyte nuclear factor 4 alpha -- AMPK 5′ adenosine monophosphate-activated protein kinase; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2016.02.048
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: IL-6 is a critical cytokine involved in malignant transformation and progression. IL-6 regulates cancer stem cell and mesenchymal stem cell formation. IL-6 induces epithelial to mesenchymal transition (EMT) in cancer. Overexpression of IL-6 is the contributing factor for chemoresistance. Abstract: Interleukin-6 (IL-6) is a cytokine present in tumor microenvironment. Elevated level of IL-6 is associated with cancer cell proliferation, angiogenesis and metastasis through fueling STAT3, MAPK and Akt signaling. It promotes epithelial to mesenchymal transition (EMT) through altered expression of N-cadherin, vimentin, snail, twist and E-cadherin leading to cancer metastasis. IL-6 boosts mammosphere formation, self-renewal of stem cells, stemness properties of cancer cells and recruitment of mesenchymal stem cells. IL-6 is also a contributing factor for multidrug resistance in cancer due to gp130/MAPK/STAT3 mediated activation of transcription factors C/EBPβ/δ, overexpression of p-glycoprotein, EMT transition and expansion of stem cells. The in-depth investigation of IL-6 mediated cellular effects and its signaling pathway can provide the new window for future research and clinical development of IL-6 targeted therapy in cancer. Thus, an overview is delivered in this review deciphering the emerging aspect of the predominant influence of IL-6 in malignant transformation, EMT, cancer-associated stem cells and chemoresistance .