FUT2 promotes the tumorigenicity and metastasis of colorectal cancer cells via the Wnt/β‑catenin pathway

Sep 24, 2026

Uploaded by hdkawk

Colorectal cancer (CRC) incidence and mortality are rising globally, yet the role of fucosyltransferase 2 (FUT2) in CRC is unclear. FUT2 expression is higher in CRC tissues than in adjacent non-tumor samples and is not linked to tumor stage. FUT2 knockdown suppresses CRC cell proliferation, migration, and invasion, induces G0/G1 arrest, and promotes apoptosis. Mechanistically, FUT2 alters β-catenin signaling by reducing β-catenin, C-myc, and cyclin D1 while increasing GSK-3β and β-catenin phosphorylation.

LanguageEnglish

CategoryHealthcare

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Pages12

Reading Time30 min

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Abstract

Introduction

Glycosylation and fucosylation in cancer

FUT2 and fucosyltransferases in tumor progression

Rationale for studying FUT2 in CRC

Wnt signaling pathway and CRC

INTERNATIONAL JOURNAL OF ONCOLOGY 62: 35, 2023 FUT2 promotes the tumorigenicity and metastasis of colorectal cancer cells via the Wnt/β‑catenin pathway PENG LIU 1‑3* , JINGYU LIU 1,2* , MENGYANG DING 1,2* , YIJING LIU 1,2 , YUE ZHANG 1,2 , XIAOMING CHEN 1,2 and ZHENXU ZHOU4 1Institute of Glycobiological Engineering and 2Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035; 3Department of Clinical Laboratory, Northwest Women's 4 and Children's Hospital, Xi'an, Shaanxi 710061; Department of Hernia and Abdominal Wall Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China Received July 15, 2022; Accepted January 9, 2023 DOI: 10.3892/ijo.2023.5483 Abstract. The incidence of colorectal cancer (CRC), a leading cause of cancer‑related mortality, has increased globally. Fucosyltransferase 2 (FUT2), catalyzing the α 1, 2‑linked fucose in mammals, has been reported to be overexpressed in several malignant cancers, including CRC. However, the effects of FUT2 on CRC remain largely unknown. Herein, it was determined that the FUT2 expression levels in CRC tissues were higher than those in adjacent non‑tumor tissues, whereas no association with tumor stage was revealed. The results of biological functional analysis revealed that FUT2 knockdown inhibited the proliferation, migration and invasion of human CRC cells. Moreover, the knockdown of FUT2 arrested the CRC cells at the G0/G1 phase and promoted the apoptosis of human CRC cells . Western blot analysis demonstrated that the expression levels of β‑catenin, C‑myc and cyclin D1 were decreased by FUT2 knockdown in CRC cells, whereas the expression of glycogen synthase kinase‑3β and the phos‑ phorylation levels of β‑catenin were increased. Additionally, Wnt2 was fucosylated by FUT2 in CRC cells. Furthermore, Correspondence to: Professor Xiaoming Chen, Institute of Glycobiological Engineering, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, 268 West Xueyuan Road, Wenzhou, Zhejiang 325035, P.R. China E‑mail: [xmc@wmu.edu.cn](xmc@wmu.edu.cn) Dr Zhenxu Zhou, Department of Hernia and Abdominal Wall Surgery, The First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Lane, Wenzhou, Zhejiang 325000, P.R. China E‑mail: [doctorzhouzhenxu@163.com](doctorzhouzhenxu@163.com) *Contributed equally Key words: fucosyltransferase 2, proliferation, metastasis, Wnt/β‑catenin pathway, colorectal cancer the knockdown of FUT2 inhibited the growth of human CRC in vivo. Overall, the findings of the present study suggest that FUT2 may be used as a potential diagnostic biomarker and therapeutic target for CRC treatment. Introduction Colorectal cancer (CRC) is the second leading cause of cancer‑related mortality and was the third most commonly diagnosed tumor in 2020, according to global cancer statis‑ tics (1,2) . The incidence and mortality associated with colorectal cancer are rapidly increasing, due to environmental factors, dietary changes, the aging population and germline genetics (3,4) . The incidence of CRC has been increasing in recent years, and the mortality rates of male and female patients with CRC in China have increased (5) . Therapies for CRC have notably improved; however, the 5‑year survival rate of patients with metastatic CRC remains extremely low, and metastatic CRC, in most cases, remains an incurable disease (6) . It is thus imperative to exploit new targets which play crucial roles in carcinogenesis. A more in‑depth under‑ standing the underlying molecular mechanisms may prove tobe helpful for the exploration of novel diagnostic or potential therapeutic targets for CRC. Glycosylation, the major post‑translational modification of proteins, regulat

FAQs

How does FUT2 expression relate to colorectal cancer tissues and tumor stage?

FUT2 expression is higher in CRC tissues than in adjacent non-tumor tissues, and no association with tumor stage is observed.

What effects does FUT2 knockdown have on CRC cells?

FUT2 knockdown inhibits CRC cell proliferation, migration, and invasion, arrests cells in the G0/G1 phase, and promotes apoptosis.

How does FUT2 influence the Wnt/β-catenin signaling pathway in CRC cells?

After FUT2 knockdown, β-catenin, C-myc, and cyclin D1 levels decrease, glycogen synthase kinase-3β and β-catenin phosphorylation increase, and FUT2 fucosylates Wnt2 in CRC cells.

Sep 24, 2026

Uploaded by hdkawk