Oncotarget

Research Papers:

Epithelial-mesenchymal transition induced by GRO-α-CXCR2 promotes bladder cancer recurrence after intravesical chemotherapy

Lu Chen, Xiu-Wu Pan, Hai Huang, Yi Gao, Qi-Wei Yang, Lin-Hui Wang, Xin-Gang Cui _ and Dan-Feng Xu

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Oncotarget. 2017; 8:45274-45285. https://doi.org/10.18632/oncotarget.16786

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Abstract

Lu Chen1,*, Xiu-Wu Pan2,3,*, Hai Huang3,*, Yi Gao3, Qi-Wei Yang2,3, Lin-Hui Wang3, Xin-Gang Cui2 and Dan-Feng Xu1

1Department of Urinary Surgery of Ruijin Hospital, Shanghai Jiaotong University, Shanghai 200025, China

2Department of Urinary Surgery of Third Affiliated Hospital, Second Military Medical University, Shanghai 201805, China

3Department of Urinary Surgery of Changzheng Hospital, Second Military Medical University, Shanghai 200003, China

*These authors have contributed equally to this work

Correspondence to:

Xin-Gang Cui, email: [email protected]

Dan-Feng Xu, email: [email protected]

Keywords: GRO-α, CXCR2, bladder cancer, epithelial-mesenchymal transition, recurrence

Received: March 24, 2016     Accepted: March 17, 2017     Published: April 03, 2017

ABSTRACT

Non-muscle invasive bladder cancers (NMIBC) are typically treated by transurethral resection with intravesical chemotherapy. However, the post-therapeutic incidence of tumor recurrence and progression to muscle invasive disease is high, and the underlying mechanism(s) remains unknown. In this study, we observed that recurrent bladder cancer cells exhibit a mesenchymal phenotype, which is initiated by the autocrine GRO-α signaling. Mechanically, the chemotherapeutic drug epidoxorubicin induces GRO-α expression in primary bladder cancer cells at G1/S phase via p38-dependent activation of NF-κB. GRO-α phosphorylation of Snail on Ser246 supports Snail’s accumulation in the nucleus, and thereby promotes transcription repression activity of Snail from E-cadherin promoters. In accordance, disrupting the GRO-α-Snail axis in NMIBC represents a promising alternative to prevent post-therapeutic tumor progression and recurrence.


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