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AKT and JNK Signaling Pathways Increase the Metastatic Potential of Colorectal Cancer Cells by Altering Transgelin Expression

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Abstract

Background

Transgelin (SM22) plays a crucial role in colorectal cancer (CRC) progression; nevertheless, its upstream regulatory mechanisms are poorly defined. AKT and JNK signaling pathways are strongly associated with tumor progression and metastasis, and there are some indications that these pathways might be involved in transgelin regulation.

Aims

To examine the role of AKT and JNK signaling in transgelin regulation in colorectal cancer progression.

Methods

Phospho-AKT (P-AKT), phospho-JNK (P-JNK), and transgelin expression were examined in one normal colon cell line (FHC) and three CRC cell lines (SW620, LoVo, and RKO) as well as in normal colon and CRC tissue samples by Western blot and qRT-PCR. Next, siRNA silencing of AKT or JNK pathways in SW620 cells was performed to examine their role in transgelin regulation. The effects of siRNA silencing on SW620 cell mobility and metastatic properties were examined by cell migration, invasion assays, and actin cytoskeleton.

Results

Transgelin, P-AKT, and P-JNK were increased in all examined cell lines. Moreover, transgelin mRNA and protein expression was especially elevated in SW620 cells. Furthermore, inhibition of Akt or JNK signaling resulted in transgelin downregulation. When transgelin, Akt, or JNK signaling was inhibited, SW620 cell migration and invasion were dramatically decreased with inhibition of actin cytoskeleton dynamics.

Conclusion

This study demonstrates, for the first time, that activated AKT and JNK signaling pathways promote the overexpression of transgelin, which potentially contributes to CRC progression and metastasis.

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Acknowledgments

We acknowledge Dr. Wang He and Dr. Bingkun Li for their assistance in reading this article.

Financial support

Ying Lin was supported by the National Natural Science Foundation of China for Young Scientists Grant (No. 30901782).

Author contributions

Huimin Zhou and Qikui Chen conceived and designed the experiments; Huimin Zhou and Yiming Zhang performed the experiments; Ying Lin analyzed the data; and Huimin Zhou wrote the paper.

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    Authors and Affiliations

    1. Department of Gastroenterology, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107. W. Yanjiang Road, Guangzhou, 510120, People’s Republic of China

      Huimin Zhou, Qikui Chen & Ying Lin

    2. Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China

      Yiming Zhang

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    1. Huimin Zhou
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    Correspondence to Qikui Chen or Ying Lin.

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    The authors declare no conflict of interest.

    Ethical standard

    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

    Informed consent

    Informed consent was obtained from all individual participants included in the study.

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    Huimin Zhou and Yiming Zhang have contributed equally to this work.

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    Zhou, H., Zhang, Y., Chen, Q. et al. AKT and JNK Signaling Pathways Increase the Metastatic Potential of Colorectal Cancer Cells by Altering Transgelin Expression. Dig Dis Sci 61, 1091–1097 (2016). https://doi.org/10.1007/s10620-015-3985-1

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    • DOI: https://doi.org/10.1007/s10620-015-3985-1

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