A novel HIF-1α/VMP1-autophagic pathway induces resistance to photodynamic therapy in colon cancer cells

Autor: Matias Exequiel Rodriguez, Viviana Rivarola, Alejandro Ropolo, Cintia Catrinacio, Maria I. Vaccaro
Rok vydání: 2017
Předmět:
0301 basic medicine
Programmed cell death
Colorectal cancer
Otras Ciencias Biológicas
medicine.medical_treatment
Photodynamic therapy
Antineoplastic Agents
COLON CANCER
Biology
Ciencias Biológicas
purl.org/becyt/ford/1 [https]
03 medical and health sciences
PHOTODYNAMIC THERAPY
Structure-Activity Relationship
Downregulation and upregulation
Radioresistance
medicine
Adjuvant therapy
Autophagy
Tumor Cells
Cultured
HIF-1ALPHA
Humans
Physical and Theoretical Chemistry
VMP1
purl.org/becyt/ford/1.6 [https]
Hypoxia-Responsive Elements
Photosensitizing Agents
Dose-Response Relationship
Drug
Membrane Proteins
medicine.disease
Hypoxia-Inducible Factor 1
alpha Subunit
030104 developmental biology
Photochemotherapy
Drug Resistance
Neoplasm
Immunology
Colonic Neoplasms
Cancer research
AUTOPHAGY
CIENCIAS NATURALES Y EXACTAS
Zdroj: CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
ISSN: 1474-9092
Popis: Colon cancer is the third most frequent cancer and the fourth most common cause of cancer-related mortality worldwide and the standard therapy is surgical resection plus adjuvant chemotherapy. Photodynamic therapy (PDT) has been proposed as adjuvant therapy because it can prevent the tumor recurrence after surgical excision in colon cancer patients. Hypoxia is a common feature in solid tumor and leads to chemo/radio resistance. Recently, it has been shown that in response to hypoxia cell can induce HIF-1α-mediated autophagy to survive in this hostile microenvironment. Moreover, hypoxia and autophagy have been implicated in resistance to antitumor PDT. However, the molecular signals by which HIF-1α induces autophagy in PDT context has not been studied yet. Here we evaluate theinterplay between HIF-1α and autophagy as well as the underlying mechanism in the PDT resistance of colon cancer cells. Our study demonstrates that HIF-1α stabilization significantly increases VMP1-related autophagy through binding to hypoxia responsive elements in VMP1 promoter. We show that HIF-1α-induced utophagy increases colon cancer cell survival as well as decreses cell death after PDT. Moreover, here we demonstrate that HIF-1α-induced autophagy is mediated by VMP1 expression, since downregulation of VMP1 by RNA interference strategy reduces HIF-1α-induced autophagy and cell survival after PDT. In conclusion, PDT induces autophagy as a survival mechanism and the induction of the novel HIF-1α/VMP1/autophagic pathway may explain, at least in part, theresistance of colon cancer cells to PDT. The knowledge of the molecular mechanisms involved in PDT resistance may lead to more accurate therapeutic strategies. Fil: Rodriguez, Matias Exequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina. Universidad Nacional de Río Cuarto; Argentina Fil: Catrinacio, Cintia Betiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina Fil: Ropolo, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina Fil: Rivarola, Viviana Alicia. Universidad Nacional de Río Cuarto; Argentina Fil: Vaccaro, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina
Databáze: OpenAIRE
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