Elevated Levels of CTRP1 in Obesity Contribute to Tumor Progression in a p53-Dependent Manner.

Rackhyun Park,Yeonjeong Park,Sim Namkoong,Minsu Jang,Junsoo Park,Yea-In Park,Jin I Lee

doi:10.3390/cancers13143619

Rackhyun Park, Yeonjeong Park + Show 5 more

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https://doi.org/10.3390/cancers13143619

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Journal: Cancers	Publication Date: Jul 19, 2021
Citations: 7	License type: CC BY 4.0

Affiliation: Yonsei University, Kangwon National University

Abstract

Simple SummaryObesity is regarded as a risk factor for various cancers. However, the molecular mechanisms linking obesity with cancer remain primarily uncharacterized. In this study, we demonstrate that CTRP1, an adiponectin paralogue, promotes tumor growth in a p53-dependent manner. Obese mice on a high-fat diet showed a higher level of CTRP1 protein in serum. It is also known that CTRP1 treatment contributes to tumor growth and cell migration. These results indicate that an elevated level of CTRP1 in obesity promotes tumor progression.Mounting evidence supports the relationship between obesity and cancer. However, the molecular mechanisms linking obesity with cancer remain largely uninvestigated. In this study, we demonstrate that the expression of C1q/TNF-related protein 1 (CTRP1), an adiponectin paralogue, contributes to tumor growth by regulating the tumor suppressor p53. In our study, obese mice on a high-fat diet showed higher serum CTRP1 levels. Through in vitro experiments, we showed that the secreted form of CTRP1 in the culture medium decreased p53 expression and p53-dependent transcription in the cells. Moreover, CTRP1 treatment enhanced colony formation and cell migration. These results collectively suggest that elevated levels of CTRP1 in obesity significantly contribute to tumor progression.

Highlights

Obesity is regarded as a risk factor for various cancers, and cancer incidence increases in the prevalence of risk factors such as obesity [1,2,3]
We used a high-fat diet-induced obese mouse model to identify the relationship between serum C1q/TNF-related protein 1 (CTRP1) levels and obesity
These results indicated that CTRP1 is involved in cell migration

Summary

Introduction

Obesity is regarded as a risk factor for various cancers, and cancer incidence increases in the prevalence of risk factors such as obesity [1,2,3]. Recent reports show how obesity is associated with an increased incidence of at least 13 different cancers, including the following: endometrial, esophageal, renal, and pancreatic adenocarcinomas, as well as hepatocellular carcinoma, gastric cardia cancer, meningioma, multiple myeloma, and colorectal, postmenopausal breast, ovarian, gallbladder, and thyroid cancers [4]. While p53 is mutated in up to 50% of human cancers, wildtype p53 is functionally inactivated in various cancers by several mechanisms, such as promoter methylation and ubiquitin-mediated degradation [10]. Growth promoting signals decrease the level of p53 to inactivate its tumor suppressor function [11]. MDM2, a typical p53 ubiquitin ligase, gets activated by Akt-mediated phosphorylation and leads to p53 degradation [12,13]

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