title: Rheb signaling and tumorigenesis: mTORC1 and new horizons.
abstract: Rheb is a conserved small GTPase that belongs to the Ras superfamily, and is mainly involved in activation of cell growth through stimulation of mTORC1 activity. Because deregulation of the Rheb/mTORC1 signaling is associated with proliferative disorders and cancer, inhibition of mTORC1 has been therapeutically approached. Although this therapy has proven antitumor activity, its efficacy is not as expected. Here, we will review the main work on the identification of the role of Rheb in cell growth, and on the relevance of Rheb in proliferative disorders, including cancer. We will also review the Rheb functions that could explain tumor resistance to therapies with mTORC1 inhibitors, and will mainly focus our discussion on mTORC1-independent Rheb functions that could also be implicated in cancer cell survival and tumorigenesis. The current progress on the understanding of the noncanonical Rheb functions prompts future studies to establish their relevance in cancer and in the context of current cancer therapies.
authors.affiliation: Laboratorio de Transducción de Señales y Cáncer, Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad De Concepción, Concepción, Chile.
authors.forename: Marisol E
authors.initials: ME
authors.lastname: Armijo
authors.affiliation: Laboratorio de Transducción de Señales y Cáncer, Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad De Concepción, Concepción, Chile.
authors.forename: Tania
authors.initials: T
authors.lastname: Campos
authors.affiliation: Laboratorio de Transducción de Señales y Cáncer, Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad De Concepción, Concepción, Chile.
authors.forename: Francisco
authors.initials: F
authors.lastname: Fuentes-Villalobos
authors.affiliation: Laboratorio de Transducción de Señales y Cáncer, Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad De Concepción, Concepción, Chile.
authors.forename: Mario E
authors.initials: ME
authors.lastname: Palma
authors.affiliation: Laboratorio de Transducción de Señales y Cáncer, Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad De Concepción, Concepción, Chile.
authors.forename: Roxana
authors.initials: R
authors.lastname: Pincheira
authors.affiliation: Laboratorio de Transducción de Señales y Cáncer, Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad De Concepción, Concepción, Chile.
authors.forename: Ariel F
authors.initials: AF
authors.lastname: Castro
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism*; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D020559:Monomeric GTP-Binding Proteins / Q000502:physiology*; D046912:Multiprotein Complexes / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology*; D000076205:Ras Homolog Enriched in Brain Protein; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*
chemical_list: D046912:Multiprotein Complexes; D009479:Neuropeptides; C490211:RHEB protein, human; D000076205:Ras Homolog Enriched in Brain Protein; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020559:Monomeric GTP-Binding Proteins
keywords: Rheb; mTORC1; mTORC1-independent Rheb functions; rapamycin resistance