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

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.

• Authors: Huimin Zhou, Yiming Zhang, Qikui Chen, Ying Lin
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 61 Issue 4 Pg. 1091-7 (Apr 2016) ISSN: 1573-2568 [Electronic] United States
• PMID: 26694173 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Microfilament Proteins
• Muscle Proteins
• transgelin
• Proto-Oncogene Proteins c-akt

Topics

• Actin Cytoskeleton (metabolism)
• Case-Control Studies
• Cell Line, Tumor
• Colon (metabolism)
• Colorectal Neoplasms (metabolism)
• Humans
• MAP Kinase Signaling System
• Microfilament Proteins (metabolism)
• Muscle Proteins (metabolism)
• Neoplasm Metastasis
• Proto-Oncogene Proteins c-akt (metabolism)