Unleashing the pathological imprinting of cancer in autoimmunity: Is ZEB1 the answer?

The intriguing scientific relationship between autoimmunity and cancer immunology have been traditionally indulged to throw spotlight on novel pathological targets. Understandably, these "slowly killing" diseases are on the opposite ends of the immune spectrum. However, the immune regulatory mechanisms between autoimmunity and cancer are not always contradictory and sometimes mirror each other based on disease stage, location, and timepoint. Moreover, the blockade of immune checkpoint molecules or signalling pathways that unleashes the immune response against cancer is being leveraged to preserve self-tolerance and treat many autoimmune disorders. Therefore, understanding the common crucial factors involved in cancer is of paramount importance to paint the autoimmune disease spectrum and validate novel drug candidates. In the current review, we will broadly describe how ZEB1, or Zinc-finger E-box Binding Homeobox 1, reinforces immune exhaustion in cancer or contributes to loss of self-tolerance in auto-immune conditions. We made an effort to exchange information about the molecular pathways and pathological responses (immune regulation, cell proliferation, senescence, autophagy, hypoxia, and circadian rhythm) that can be regulated by ZEB1 in the context of autoimmunity. This will help untwine the intricate and closely postured pathogenesis of ZEB1, that is less explored from the perspective of autoimmunity than its counterpart, cancer. This review will further consider several approaches for targeting ZEB1 in autoimmunity.

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