title: Endoplasmic reticulum-mediated unfolded protein response and mitochondrial apoptosis in cancer.
abstract: Abrogation of endoplasmic reticulum (ER) protein folding triggered by exogenous or endogenous factors, stimulates a cellular stress response, termed ER stress. ER stress re-establishes ER homeostasis through integrated signaling termed the ER-unfolded protein response (UPRER). In the presence of severe toxic or prolonged ER stress, the pro-survival function of UPRERis transformed into a lethal signal transmitted to and executed through mitochondria. Mitochondria are key for both apoptotic and autophagic cell death. Thus ER is vital in sensing and coordinating stress pathways to maintain overall physiological homeostasis. However, this function is deregulated in cancer, resulting in resistance to apoptosis induction in response to various stressors including therapeutic agents. Here we review the connections between ER stress and mitochondrial apoptosis, describing potential cancer therapeutic targets.
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, United States.
authors.forename: Tariq A
authors.initials: TA
authors.lastname: Bhat
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, United States.
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Chaudhary
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, United States.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, United States.
authors.forename: Jordan
authors.initials: J
authors.lastname: O'Malley
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, United States.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Inigo
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, United States.
authors.forename: Rahul
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, United States.
authors.forename: Neelu
authors.initials: N
authors.lastname: Yadav
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, United States. Electronic address: dhyan.chandra@roswellpark.org.
authors.forename: Dhyan
authors.initials: D
authors.lastname: Chandra
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000473:pathology*; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000473:pathology*; D009369:Neoplasms / Q000473:pathology*; D017510:Protein Folding; D015398:Signal Transduction / Q000502:physiology; D056811:Unfolded Protein Response / Q000502:physiology*
keywords: Apoptosis; Autophagy; Endoplasmic reticulum; Mitochondria; Unfolded protein response