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CCR9–CCL25 interaction suppresses apoptosis of lung cancer cells by activating the PI3K/Akt pathway

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Abstract

CC chemokine receptor-9 (CCR9) is highly expressed in non-small cell lung cancer (NSCLC) tissues and cell lines. However, the biological functions and the signals elicited by the interaction between CCR9 and its natural ligand CCL25 in NSCLC are unknown. Here, we selectively depleted CCR9 and inhibited CCR9–CCL25 interaction in NSCLC cells using small recombinant lentivirus-mediated miRNA, and investigated the tumorigenic effects in vitro and in vivo. Compromised CCR9–CCL25 interaction promoted apoptosis in NSCLC cells by activating phosphoinositide 3-kinase (PI3K)/Akt in vitro. In addition, we showed that CCR9–CCL25 interaction mediated the activation of the PI3K/Akt pathway in NSCLC cells, resulting in the up-regulation of anti-apoptotic proteins, as well as the down-regulation of apoptotic proteins in a PI3K-/Akt-dependent manner. These CCR9–CCL25-mediated effects were abrogated in the presence of a PI3K inhibitor (wortmannin 10 nM) or by inhibiting the CCR9–CCL25 interaction through CCR9 silencing, which also suggested that the biological function of CCR9–CCL25 was mainly regulated by PI3K. In vivo studies also demonstrated a significantly lower tumor burden in mice receiving CCR9-silence cells than those in mice receiving control cells. Together, these data suggested that CCR9–CCL25 interaction induced tumorigenesis of NSCLC cells and that this induction might be accomplished through the activation of the PI3K/Akt pathway. These findings may lead to a better understanding of the biological effects of CCR9–CCL25 interaction and provide clues for identifying novel therapeutic and preventive molecular markers for NSCLC.

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Abbreviations

CCR9:

CC chemokine receptor-9

NSCLC:

Non-small cell lung cancer

PI3K:

Phosphoinositide 3-kinase

GPCRs:

G protein-coupled receptors

TECK:

Thymus-expressed chemokine

SCCs:

Squamous cell carcinomas

ACs:

Adenocarcinomas

GFP:

Green fluorescent protein

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Acknowledgments

This work was supported by the Scientific Research and Technological Development Projects of Guangxi, China (No. 0816004-8). We thank the scientific research experiment center of the People’s Hospital of Guangxi Zhuang Autonomous Region for technical support.

Conflict of interest

The authors have no conflict of interest.

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Authors and Affiliations

  1. The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China

    Baijun Li, Yonglong Zhong, Jiao Lan, Xiangwei Li & Hui Lin

  2. Renmin Hospital of Wuhan University, Wuhan, 430060, China

    Zhiwei Wang

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  1. Baijun Li
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Correspondence to Hui Lin.

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Li, B., Wang, Z., Zhong, Y. et al. CCR9–CCL25 interaction suppresses apoptosis of lung cancer cells by activating the PI3K/Akt pathway. Med Oncol 32, 66 (2015). https://doi.org/10.1007/s12032-015-0531-0

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