Abstract
One of the striking characteristics of cancer cells is their phenotypic diversity and ability to switch phenotypes in response to environmental fluctuations. Such phenotypic changes (e.g. from drug-sensitive to drug-resistant), which are critical for survival and proliferation, are widely believed to arise due to mutations in the cancer cell’s genome. However, there is growing concern that such a deterministic view is not entirely consistent with multiple lines of evidence which indicate that cancer can arise in the absence of mutations and can even be reversed to normalcy despite the mutations. In this Commentary, we wish to present an alternate view that highlights how stochasticity in protein interaction networks (PINs) may play a key role in cancer initiation and progression. We highlight the potential role of intrinsically disordered proteins (IDPs) and submit that targeting IDPs can lead to new insights and treatment protocols for cancer.
Highlights
One of the striking characteristics of cancer cells is their phenotypic diversity and ability to switch phenotypes in response to environmental fluctuations
In light of the incessant deluge of data that often show meager correlations to cancer cause, diagnosis or prognosis, one wonders whether cancer is a genetic disease and whether all cancers arise as a result of changes in the cancer cell’s genome as is commonly believed [1,2]
Conventional wisdom suggests that cancer cells contain so many mutations that their reversal to normalcy is unlikely
Summary
Stochastic gene expression, disruption of tissue averaging effects and cancer as a disease of development. Mahmoudabadi G, Rajagopalan K, Getzenberg RH, Hannenhalli S, Rangarajan G, Kulkarni P: Intrinsically disordered proteins and conformational noise: implications in cancer. Vavouri T, Semple JI, Garcia-Verdugo R, Lehner B: Intrinsic protein disorder and interaction promiscuity are widely associated with dosage sensitivity. Tompa P, Csermely P: The role of structural disorder in the function of RNA and protein chaperones. Cumberworth A, Lamour G, Babu MM, Gsponer J: Promiscuity as a functional trait: intrinsically disordered regions as central players of interactomes. Rajagopalan K, Mooney SM, Parekh N, Getzenberg RH, Kulkarni P: A majority of the cancer/testis antigens are intrinsically disordered proteins.
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