Browsing by Author "Sooro, MA"

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    Autophagic regulation of P62 is critical for cancer therapy
    (International Journal of Molecular Sciences, 2018-05-08) Ariful, Islam; Sooro, MA
    Sequestosome1 (p62/SQSTM 1) is a multidomain protein that interacts with the autophagy machinery as a key adaptor of target cargo. It interacts with phagophores through the LC3-interacting (LIR) domain and with the ubiquitinated protein aggregates through the ubiquitin-associated domain (UBA) domain. It sequesters the target cargo into inclusion bodies by its PB1 domain. This protein is further the central hub that interacts with several key signaling proteins. Emerging evidence implicates p62 in the induction of multiple cellular oncogenic transformations. Indeed, p62 upregulation and/or reduced degradation have been implicated in tumor formation, cancer promotion as well as in resistance to therapy. It has been established that the process of autophagy regulates the levels of p62. Autophagy-dependent apoptotic activity of p62 is recently being reported. It is evident that p62 plays a critical role in both autophagy and apoptosis. Therefore in this review we discuss the role of p62 in autophagy, apoptosis and cancer through its different domains and outline the importance of modulating cellular levels of p62 in cancer therapeutics.
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    Targeting EGFR-mediated autophagy as a potential strategy for cancer therapy
    (Global Cancer Control, 2018-03) Sooro, MA; Zhang, Ni; Zhang, P
    Autophagy is a naturally occurring programed cellular catabolic process stimulated by cellular stress for energy homeostasis maintenance and elimination of harmful substances. It mostly works as pro-survival mechanism but on the other hand deregulation of autophagy has been linked to non-apoptotic cell death known as “type II programed cell death.” Emerging evidences indicate that EGFR (epidermal growth factor receptor)-mediated RAS/RAF/MEK/ERK signaling pathway plays a critical role in the induction of autophagy in various tumors. It has further been established that this signaling pathway is also involved in several other anti-proliferative events such as apoptosis and senescence. However, the signaling pathway activity and effects are highly dependent on the cell type and the stimulus. It is currently being evident that autophagy induction by RAS/RAF/ MEK/ERK pathway through small molecules may be a potential therapeutic strategy for cancer. However, to our best knowledge, the role of EGFR-mediated RAS/RAF/MEK/ERK signaling pathway in autophagy-mediated cell death and survival have not previously been reviewed. In this review, we discuss the current state of knowledge on how RAS/RAF/MEK/ERK signaling pathway regulates autophagy and the role of this EGFR-mediated autophagy in diseases. We further examine the cross-talk between this EGFR-mediated autophagy and apoptosis as well as how this process is currently being utilized for cancer treatment and suggest promoting autophagy-related cell death by small molecules may be exploited to design better therapeutic strategies for early stage and locally advanced tumors