IL-32α suppresses colorectal cancer development via TNFR1-mediated death signaling

Hyung-Mun Yun; Kyung-Ran Park; Eun-Cheol Kim; Sang Bae Han; Do Young Yoon; Jin Tae Hong

doi:10.18632/oncotarget.3197

IL-32α suppresses colorectal cancer development via TNFR1-mediated death signaling

Oncotarget. 2015 Apr 20;6(11):9061-72. doi: 10.18632/oncotarget.3197.

Authors

Hyung-Mun Yun¹, Kyung-Ran Park¹, Eun-Cheol Kim¹, Sang Bae Han², Do Young Yoon³, Jin Tae Hong²

Affiliations

¹ Department of Maxillofacial Tissue Regeneration, School of Dentistry and Research Center for Tooth & Periodontal Regeneration (MRC), Kyung Hee University, Seoul 130-701, Republic of Korea.
² College of Pharmacy and Medical Research Center, Chungbuk National University, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
³ Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 150-716, Republic of Korea.

Abstract

Inflammation is associated with cancer-prone microenvironment, leading to cancer. IL-32 is expressed in chronic inflammation-linked human cancers. To investigate IL-32α in inflammation-linked colorectal carcinogenesis, we generated a strain of mice, expressing IL-32 (IL-32α-Tg). In IL-32α-Tg mice, azoxymethane (AOM)-induced colon cancer incidence was decreased, whereas expression of TNFR1 and TNFR1-mediated apoptosis was increased. Also, IL-32α increased ROS production to induce prolonged JNK activation. In colon cancer patients, IL-32α and TNFR1 were increased. These findings indicate that IL-32α suppressed colon cancer development by promoting the death signaling of TNFR1.

Keywords: IL-32α; RIP1; TNFR1; colon cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / etiology
Adenocarcinoma / metabolism*
Adenocarcinoma / pathology
Animals
Apoptosis
Azoxymethane
Cell Line, Tumor
Colonic Neoplasms / chemically induced
Colonic Neoplasms / metabolism
Colonic Neoplasms / prevention & control
Colorectal Neoplasms / etiology
Colorectal Neoplasms / metabolism*
Colorectal Neoplasms / pathology
Enzyme Activation
Humans
Inflammation / chemically induced
Inflammation / complications*
Inflammation / metabolism
Interleukins / genetics
Interleukins / physiology*
JNK Mitogen-Activated Protein Kinases / metabolism
Mice
Mice, Transgenic
Neoplasm Proteins / biosynthesis
Neoplasm Proteins / genetics
Neoplasm Proteins / physiology*
Reactive Oxygen Species
Receptors, Tumor Necrosis Factor, Type I / analysis
Receptors, Tumor Necrosis Factor, Type I / biosynthesis
Receptors, Tumor Necrosis Factor, Type I / genetics
Receptors, Tumor Necrosis Factor, Type I / physiology*
Recombinant Fusion Proteins / metabolism
Signal Transduction*

Substances

IL32 protein, human
Interleukins
Neoplasm Proteins
Reactive Oxygen Species
Receptors, Tumor Necrosis Factor, Type I
Recombinant Fusion Proteins
Tnfrsf1a protein, mouse
JNK Mitogen-Activated Protein Kinases
Azoxymethane