Involvement of PDGFR‐integrin interactions in the regulation of anoikis resistance in glioblastoma progression

The interactions between platelet‐derived growth factor/PDGF receptor and integrin signaling are crucial for cells to respond to extracellular stimuli. Integrin interactions with PDGFR within the lipid rafts activate downstream cellular signaling pathways that regulate cell proliferation, cell migration, cell differentiation, and cell death processes. The mechanisms underlying PDGFR activation mediated receptor internalization, interactions with other cell‐surface receptors, particularly extracellular matrix receptors, integrins, and how these cellular mechanisms switch on anchorage‐independent cell survival, leading to anoikis resistance are discussed. The role of regulatory molecules such as noncoding RNAs, that can modulate several molecular and cellular processes, including autophagy, in the acquisition of anoikis resistance is also discussed. Overall, the review provides a new perspective on a complex interplay of regulatory cellular machineries involving autophagy, noncoding RNAs and cellular mechanisms of PDGFR activation, PDGFR‐integrin interactions, and involvement of lipids rafts in the acquisition of anoikis resistance that regulates glioblastoma progression along with potential future strategies to develop novel therapeutics for glioblastoma multiforme. Anoikis resistance is one of the leading cause of tumor progression and drug resistance in solid tumors, and anchorage independency leads to anoikis resistance and helps the tumor cells to grow, invade, and metastasize to distant organs and tissues. Overexpression of various cell adhesion molecules, such as Integrin receptors, and also growth factors and their receptor molecules, has been reported in the majority of solid tumors during anoikis resistance. Autophagy is one of the many cellular processes that has been shown to be upregulated in various solid tumors during the steps of tumorigenesis including anchorage independency. Integrins, growth factor and their receptors, and autophagy have been extensively targeted in cancer therapeutics. Noncoding RNAs have emerged as one of the potent therapeutic targets in recent years.