title: Lack of STAT6 Attenuates Inflammation and Drives Protection against Early Steps of Colitis-Associated Colon Cancer.
abstract: Colitis-associated colon cancer (CAC) is one of the most common malignant neoplasms and a leading cause of death. The immunologic factors associated with CAC development are not completely understood. Signal transducer and activator of transcription 6 (STAT6) is part of an important signaling pathway for modulating intestinal immune function and homeostasis. However, the role of STAT6 in colon cancer progression is unclear. Following CAC induction in wild-type (WT) and STAT6-deficient mice (STAT6-/-), we found that 70% of STAT6-/-mice were tumor-free after 8 weeks, whereas 100% of WT mice developed tumors. STAT6-/-mice displayed fewer and smaller colorectal tumors than WT mice; this reduced tumorigenicity was associated with decreased proliferation and increased apoptosis in the colonic mucosa in the early steps of tumor progression. STAT6-/-mice also exhibited reduced inflammation, diminished concentrations COX2 and nuclear β-catenin protein in the colon, and decreased mRNA expression of IL17A and TNFα, but increased IL10 expression when compared with WT mice. Impaired mucosal expression of CCL9, CCL25, and CXCR2 was also observed. In addition, the number of circulating CD11b+Ly6ChiCCR2+monocytes and CD11b+Ly6ClowLy6G+granulocytes was both decreased in a STAT6-dependent manner. Finally, WT mice receiving a STAT6 inhibitorin vivoconfirmed a significant reduction in tumor load as well as less intense signs of CAC. Our results demonstrate that STAT6 is critical in the early steps of CAC development for modulating inflammatory responses and controlling cell recruitment and proliferation. Thus, STAT6 may represent a promising target for CAC treatment.Cancer Immunol Res; 5(5); 385-96. ©2017 AACR.
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Edo. De México, Mexico.|Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Edo. De México, Mexico.
authors.forename: Sonia A
authors.initials: SA
authors.lastname: Leon-Cabrera
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Edo. De México, Mexico.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Molina-Guzman
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Edo. De México, Mexico.
authors.forename: Yael G
authors.initials: YG
authors.lastname: Delgado-Ramirez
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Edo. De México, Mexico.
authors.forename: Armando
authors.initials: A
authors.lastname: Vázquez-Sandoval
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Edo. De México, Mexico.
authors.forename: Yadira
authors.initials: Y
authors.lastname: Ledesma-Soto
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Edo. De México, Mexico.
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Pérez-Plasencia
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Edo. De México, Mexico.
authors.forename: Yolanda I
authors.initials: YI
authors.lastname: Chirino
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Edo. De México, Mexico.
authors.forename: Norma L
authors.initials: NL
authors.lastname: Delgado-Buenrostro
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Edo. De México, Mexico.
authors.forename: Miriam
authors.initials: M
authors.lastname: Rodríguez-Sosa
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Edo. De México, Mexico.|Laboratorio Nacional en Salud, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Mexico.
authors.forename: Felipe
authors.initials: F
authors.lastname: Vaca-Paniagua
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Edo. De México, Mexico.
authors.forename: Federico
authors.initials: F
authors.lastname: Ávila-Moreno
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Edo. De México, Mexico.
authors.forename: Emma B
authors.initials: EB
authors.lastname: Gutierrez-Cirlos
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Edo. De México, Mexico.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Arias-Romero
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Edo. De México, Mexico. literrazas@unam.mx.|Laboratorio Nacional en Salud, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Mexico.
authors.forename: Luis I
authors.initials: LI
authors.lastname: Terrazas
mesh_terms: D000818:Animals; D017209:Apoptosis; D001397:Azoxymethane; D049109:Cell Proliferation; D003092:Colitis / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D016264:Dextran Sulfate; D005260:Female; D007249:Inflammation; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D051176:beta Catenin; D016264:Dextran Sulfate; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D001397:Azoxymethane