STAT3 enhances radiation-induced tumor migration, invasion and stem-like properties of bladder cancer

Abstract

Bladder cancer (BCa) is the most common cancer of the human urinary system, and is associated with poor patient prognosis and a high recurrence rate. Cancer stem cells (CSCs) are the primary cause of tumor recurrence and metastasis, possessing self-renewal properties and resistance to radiation therapy. Our previous studies indicated that phosphorylated signal transduction and transcription activator 3 (STAT3) may be a potential biomarker to predict radiation tolerance and tumor recurrence in patients with BCa, following conventional radiotherapy. The aim of the present study was to investigate the underlying mechanism of STAT3 in the radio-resistance of BCa cells. It was found that fractionated irradiation promoted the activation of two STAT3-associated CSCs signaling pathways in BCa cells, namely suppressor of variegation 3-9 homolog 1/GATA binding protein 3/STAT3 and Janus kinase 2/STAT3. Surviving cells exhibited elevated migratory and invasive abilities, enhanced CSC-like characteristics and radio-resistance. Furthermore, knockdown of STAT3 expression or inhibition of STAT3 activation markedly decreased the self-renewal ability and tumorigenicity of radiation-resistant BCa cells. Kaplan-Meier analysis revealed that decreased STAT3 mRNA levels were associated with increased overall survival times in patients with BCa. Taken together, these data indicated that STAT3 may be an effective therapeutic target for inhibiting the progression, metastasis and recurrence of BCa in patients receiving radiotherapy.

EZH2 targeting to improve the sensitivity of acquired radio-resistance bladder cancer cells

“…However, only T24R cells formed tumors after inoculation in our experiments ( Fig. 6 A) [13] . It was found that untreated tumors took a period of 2 weeks (14 days) to reach around 800mm 3 .…”

STAT3 and Its Pathways Dysregulation – Underestimated Role in Urological Tumors

“…Fractional irradiation enhanced the invasiveness, motility and stem-like characteristics of bladder cancer cells. Responsibility for this effect was assigned to STAT3 which was previously reported to be significantly phosphorylated in irradiated cells [105]. Knockdown of STAT3 brought a loss of tumor formation in immunodeficient mice.…”

Noncoding RNAs as regulators of STAT3 pathway in gastrointestinal cancers: Roles in cancer progression and therapeutic response

“…48 Wang et al demonstrated that STAT3 increases the radiation-driven motility and stem-like features of bladder cancer. 49 Guanylate-binding protein 2 (GBP2) is involved in offering immunity against pathogens and is overexpressed in glioblastoma multiforme (especially in the mesenchymal phenotype) which is associated with poor clinical outcomes. GBP2 was found to increase invasion through STAT3/fibronectin axis.…”

“…STAT3 and glucocorticoid receptors cooperatively activate the expression signature of basal‐like triple‐negative breast cancer which contributes to the dismal prognosis and combinational use of inhibitors of these two transcription factors resulting in growth‐inhibitory effects in cell lines and patient‐derived organoid models 48 . Wang et al demonstrated that STAT3 increases the radiation‐driven motility and stem‐like features of bladder cancer 49 . Guanylate‐binding protein 2 (GBP2) is involved in offering immunity against pathogens and is overexpressed in glioblastoma multiforme (especially in the mesenchymal phenotype) which is associated with poor clinical outcomes.…”