SOX4 is a pivotal regulator of tumorigenesis in differentiated thyroid cancer

Chi Yu Kuo; Yi Chiung Hsu; Chien Liang Liu; Ying Syuan Li; Shao Chiang Chang; Shih Ping Cheng

doi:10.1016/j.mce.2023.112062

SOX4 is a pivotal regulator of tumorigenesis in differentiated thyroid cancer

Chi Yu Kuo, Yi Chiung Hsu, Chien Liang Liu, Ying Syuan Li, Shao Chiang Chang, Shih Ping Cheng

Department of Biomedical Sciences and Engineering

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

The SOX family consists of about 20 transcription factors involved in embryonic development, reprogramming, and cell fate determination. In this study, we demonstrated that SOX4 was significantly upregulated in differentiated thyroid cancer. Immunohistochemical analysis revealed that high SOX4 expression was associated with papillary histology, extrathyroidal extension, lymph node metastasis, and advanced disease stage. Patients whose tumors exhibited high SOX4 expression had a shorter recurrence-free survival, though significance was lost in multivariate Cox regression analysis. SOX4 silencing in thyroid cancer cells slowed cell growth, attenuated clonogenicity, and suppressed anoikis resistance. Additionally, SOX4 knockdown impeded xenograft tumor growth in nude mice. Knockdown of SOX4 expression was accompanied by reduced phosphorylation of AKT and ERK. Furthermore, CRABP2 expression correlated with SOX4 expression, and SOX4 silencing decreased CRABP2 expression and its downstream effectors such as integrin β1 and β4. These results indicate that SOX4 has both prognostic and therapeutic implications in differentiated thyroid cancer, and targeting SOX4 may modulate tumorigenic processes in the thyroid.

Original language	English
Article number	112062
Journal	Molecular and Cellular Endocrinology
Volume	578
DOIs	https://doi.org/10.1016/j.mce.2023.112062
State	Published - 1 Dec 2023

Keywords

CRABP2
SOX4
Thyroid cancer
Tumorigenesis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.mce.2023.112062

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title = "SOX4 is a pivotal regulator of tumorigenesis in differentiated thyroid cancer",

abstract = "The SOX family consists of about 20 transcription factors involved in embryonic development, reprogramming, and cell fate determination. In this study, we demonstrated that SOX4 was significantly upregulated in differentiated thyroid cancer. Immunohistochemical analysis revealed that high SOX4 expression was associated with papillary histology, extrathyroidal extension, lymph node metastasis, and advanced disease stage. Patients whose tumors exhibited high SOX4 expression had a shorter recurrence-free survival, though significance was lost in multivariate Cox regression analysis. SOX4 silencing in thyroid cancer cells slowed cell growth, attenuated clonogenicity, and suppressed anoikis resistance. Additionally, SOX4 knockdown impeded xenograft tumor growth in nude mice. Knockdown of SOX4 expression was accompanied by reduced phosphorylation of AKT and ERK. Furthermore, CRABP2 expression correlated with SOX4 expression, and SOX4 silencing decreased CRABP2 expression and its downstream effectors such as integrin β1 and β4. These results indicate that SOX4 has both prognostic and therapeutic implications in differentiated thyroid cancer, and targeting SOX4 may modulate tumorigenic processes in the thyroid.",

keywords = "CRABP2, SOX4, Thyroid cancer, Tumorigenesis",

author = "Kuo, {Chi Yu} and Hsu, {Yi Chiung} and Liu, {Chien Liang} and Li, {Ying Syuan} and Chang, {Shao Chiang} and Cheng, {Shih Ping}",

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doi = "10.1016/j.mce.2023.112062",

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T1 - SOX4 is a pivotal regulator of tumorigenesis in differentiated thyroid cancer

AU - Kuo, Chi Yu

AU - Hsu, Yi Chiung

AU - Liu, Chien Liang

AU - Li, Ying Syuan

AU - Chang, Shao Chiang

AU - Cheng, Shih Ping

PY - 2023/12/1

Y1 - 2023/12/1

N2 - The SOX family consists of about 20 transcription factors involved in embryonic development, reprogramming, and cell fate determination. In this study, we demonstrated that SOX4 was significantly upregulated in differentiated thyroid cancer. Immunohistochemical analysis revealed that high SOX4 expression was associated with papillary histology, extrathyroidal extension, lymph node metastasis, and advanced disease stage. Patients whose tumors exhibited high SOX4 expression had a shorter recurrence-free survival, though significance was lost in multivariate Cox regression analysis. SOX4 silencing in thyroid cancer cells slowed cell growth, attenuated clonogenicity, and suppressed anoikis resistance. Additionally, SOX4 knockdown impeded xenograft tumor growth in nude mice. Knockdown of SOX4 expression was accompanied by reduced phosphorylation of AKT and ERK. Furthermore, CRABP2 expression correlated with SOX4 expression, and SOX4 silencing decreased CRABP2 expression and its downstream effectors such as integrin β1 and β4. These results indicate that SOX4 has both prognostic and therapeutic implications in differentiated thyroid cancer, and targeting SOX4 may modulate tumorigenic processes in the thyroid.

AB - The SOX family consists of about 20 transcription factors involved in embryonic development, reprogramming, and cell fate determination. In this study, we demonstrated that SOX4 was significantly upregulated in differentiated thyroid cancer. Immunohistochemical analysis revealed that high SOX4 expression was associated with papillary histology, extrathyroidal extension, lymph node metastasis, and advanced disease stage. Patients whose tumors exhibited high SOX4 expression had a shorter recurrence-free survival, though significance was lost in multivariate Cox regression analysis. SOX4 silencing in thyroid cancer cells slowed cell growth, attenuated clonogenicity, and suppressed anoikis resistance. Additionally, SOX4 knockdown impeded xenograft tumor growth in nude mice. Knockdown of SOX4 expression was accompanied by reduced phosphorylation of AKT and ERK. Furthermore, CRABP2 expression correlated with SOX4 expression, and SOX4 silencing decreased CRABP2 expression and its downstream effectors such as integrin β1 and β4. These results indicate that SOX4 has both prognostic and therapeutic implications in differentiated thyroid cancer, and targeting SOX4 may modulate tumorigenic processes in the thyroid.

KW - CRABP2

KW - SOX4

KW - Thyroid cancer

KW - Tumorigenesis

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U2 - 10.1016/j.mce.2023.112062

DO - 10.1016/j.mce.2023.112062

M3 - 期刊論文

C2 - 37673293

AN - SCOPUS:85169936208

SN - 0303-7207

VL - 578

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

M1 - 112062

ER -

SOX4 is a pivotal regulator of tumorigenesis in differentiated thyroid cancer

Abstract

Keywords

UN SDGs

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