title: Targeting Tumor Initiating Cells through Inhibition of Cancer Testis Antigens and Notch Signaling: A Hypothesis.
abstract: Tumor initiating cells (TICs) differ from normal stem cells (SCs) in their ability to initiate tumorigenesis, invasive growth, metastasis and the acquisition of chemo and/or radio-resistance. Over the past years, several studies have indicated the potential role of the Notch system as a key regulator of cellular stemness and tumor development. Furthermore, the expression of cancer testis antigens (CTA) in TICs, and their role in SC differentiation and biology, has become an important area of investigation. Here, we propose a model in which CTA expression and Notch signaling interacts to maintain the sustainability of self-replicating tumor populations, ultimately leading to the development of metastasis, drug resistance and cancer progression. We hypothesize that Notch-CTA interactions in TICs offer a novel opportunity for meaningful therapeutic interventions in cancer.
authors.affiliation: Department of Health Sciences, Università degli Studi di Milano , Milano , Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Colombo
authors.forename: Leonardo
authors.initials: L
authors.lastname: Mirandola
authors.forename: Adair
authors.initials: A
authors.lastname: Reidy
authors.forename: Natallia
authors.initials: N
authors.lastname: Suvorava
authors.forename: Venu
authors.initials: V
authors.lastname: Konala
authors.forename: Raffaella
authors.initials: R
authors.lastname: Chiaramonte
authors.forename: Fabio
authors.initials: F
authors.lastname: Grizzi
authors.forename: Rakhshanda Layeequr
authors.initials: RL
authors.lastname: Rahman
authors.forename: Marjorie R
authors.initials: MR
authors.lastname: Jenkins
authors.forename: Diane D
authors.initials: DD
authors.lastname: Nugyen
authors.forename: Scott
authors.initials: S
authors.lastname: Dalhbeck
authors.forename: Everardo
authors.initials: E
authors.lastname: Cobos
authors.forename: Jose A
authors.initials: JA
authors.lastname: Figueroa
authors.forename: Maurizio
authors.initials: M
authors.lastname: Chiriva-Internati
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D063646:Carcinogenesis; D000066673:Cell Self Renewal; D019008:Drug Resistance, Neoplasm; D006801:Humans; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D014411:Neoplastic Stem Cells / Q000276:immunology*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000951:Antigens, Neoplasm; D051880:Receptors, Notch
keywords: cancer; cancer testis antigens; notch signaling; stem cells