SSH3 Facilitates Colorectal Cancer Cell Invasion and Metastasis by Affecting Signaling Cascades Involving LIMK1/Rac1

Overview

Journal Am J Cancer Res

Specialty Oncology

Date 2019 Jun 21

PMID 31218112

Citations 10

Authors

Yu-Han Hu

Yan-Xia Lu

Zhe-Ying Zhang

Jian-Ming Zhang

Wen-Juan Zhang

Lin Zheng

Wei-Hao Lin

Wei Zhang

Xue-Nong Li

Affiliations

Soon will be listed here.

Abstract

Slingshot phosphatase 3 (SSH3) is a member of the SSH phosphatase family that regulates actin filament dynamics. However, its role in cancer metastasis is relatively unclear compared to that of SSH1. Here, we showed that SSH3 was upregulated in colorectal cancer (CRC). Of note, SSH3 was upregulated in the tumor thrombus and lymph node metastasis compared with that in paired primary CRC tissues. High SSH3 expression was associated with the aggressive phenotype of CRC and may be an independent prognostic factor for the poor survival of patients with CRC. SSH3 significantly enhanced the invasion and metastasis of CRC cells in vitro and in vivo. Moreover, SSH3 regulated the remodeling of actin, which is involved in the cytoskeleton signaling pathway, through its interaction with LIMK1/Rac1 and subsequently promoted CRC cell invasion and metastasis. Our data elucidate an important role for SSH3 in the progression of CRC, and SSH3 may be considered a potential therapeutic target for CRC.

Citing Articles

Potential role of TWIST1 and its methylation in bladder urothelial carcinoma.

Wan M, Meng H, Li H Transl Cancer Res. 2024; 13(11):6070-6086.

PMID: 39697731 PMC: 11651768. DOI: 10.21037/tcr-24-1029.

Plasma extracellular vesicle long RNA profiling identifies a predictive signature for immunochemotherapy efficacy in lung squamous cell carcinoma.

Zhang X, Liao J, Yang W, Li Q, Wang Z, Yu H Front Immunol. 2024; 15:1421604.

PMID: 39161762 PMC: 11331801. DOI: 10.3389/fimmu.2024.1421604.

SSH3 promotes pancreatic cancer proliferation and migration by activating the notch signaling pathway.

Yang C, Quan G, Zhang S, Jiang J Am J Cancer Res. 2024; 14(4):1815-1830.

PMID: 38726290 PMC: 11076266. DOI: 10.62347/DAZV7194.

Impact of Protein Phosphatase Expressions on the Prognosis of Hepatocellular Carcinoma Patients.

Mestareehi A, Abu-Farsakh N ACS Omega. 2024; 9(9):10299-10331.

PMID: 38463290 PMC: 10918787. DOI: 10.1021/acsomega.3c07787.

PDZ and LIM Domain-Encoding Genes: Their Role in Cancer Development.

Jiang X, Xu Z, Jiang S, Wang H, Xiao M, Shi Y Cancers (Basel). 2023; 15(20).

PMID: 37894409 PMC: 10605254. DOI: 10.3390/cancers15205042.

References

Niwa R, Nagata-Ohashi K, Takeichi M, Mizuno K, Uemura T . Control of actin reorganization by Slingshot, a family of phosphatases that dephosphorylate ADF/cofilin. Cell. 2002; 108(2):233-46. DOI: 10.1016/s0092-8674(01)00638-9. View

Raftopoulou M, Hall A . Cell migration: Rho GTPases lead the way. Dev Biol. 2003; 265(1):23-32. DOI: 10.1016/j.ydbio.2003.06.003. View

Nishita M, Tomizawa C, Yamamoto M, Horita Y, Ohashi K, Mizuno K . Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration. J Cell Biol. 2005; 171(2):349-59. PMC: 2171197. DOI: 10.1083/jcb.200504029. View

Wang L, Xiang J, Yan M, Zhang Y, Zhao Y, Yue C . The mitotic kinase Aurora-A induces mammary cell migration and breast cancer metastasis by activating the Cofilin-F-actin pathway. Cancer Res. 2010; 70(22):9118-28. DOI: 10.1158/0008-5472.CAN-10-1246. View

Chaffer C, Weinberg R . A perspective on cancer cell metastasis. Science. 2011; 331(6024):1559-64. DOI: 10.1126/science.1203543. View

Wickstead B, Gull K . The evolution of the cytoskeleton. J Cell Biol. 2011; 194(4):513-25. PMC: 3160578. DOI: 10.1083/jcb.201102065. View

Hall A . Rho family GTPases. Biochem Soc Trans. 2012; 40(6):1378-82. DOI: 10.1042/BST20120103. View

Rajakyla E, Vartiainen M . Rho, nuclear actin, and actin-binding proteins in the regulation of transcription and gene expression. Small GTPases. 2014; 5:e27539. PMC: 4114923. DOI: 10.4161/sgtp.27539. View

Lu Y, Yuan L, Xue X, Zhou M, Liu Y, Zhang C . Regulation of colorectal carcinoma stemness, growth, and metastasis by an miR-200c-Sox2-negative feedback loop mechanism. Clin Cancer Res. 2014; 20(10):2631-42. DOI: 10.1158/1078-0432.CCR-13-2348. View

10.

LeBleu V, OConnell J, Gonzalez Herrera K, Wikman H, Pantel K, Haigis M . PGC-1α mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis. Nat Cell Biol. 2014; 16(10):992-1003, 1-15. PMC: 4369153. DOI: 10.1038/ncb3039. View

11.

Yuan L, Zhou C, Lu Y, Hong M, Zhang Z, Zhang Z . IFN-γ-mediated IRF1/miR-29b feedback loop suppresses colorectal cancer cell growth and metastasis by repressing IGF1. Cancer Lett. 2015; 359(1):136-47. DOI: 10.1016/j.canlet.2015.01.003. View

12.

Wang Y, Kuramitsu Y, Kitagawa T, Baron B, Yoshino S, Maehara S . Cofilin-phosphatase slingshot-1L (SSH1L) is over-expressed in pancreatic cancer (PC) and contributes to tumor cell migration. Cancer Lett. 2015; 360(2):171-6. DOI: 10.1016/j.canlet.2015.02.015. View

13.

Zhan H, Ma J, Ruan F, Bedaiwy M, Peng B, Wu R . Elevated phosphatase of regenerating liver 3 (PRL-3) promotes cytoskeleton reorganization, cell migration and invasion in endometrial stromal cells from endometrioma. Hum Reprod. 2016; 31(4):723-33. DOI: 10.1093/humrep/dew015. View

14.

Zhang Z, Zhou C, Chang Y, Zhang Z, Hu Y, Zhang F . Long non-coding RNA CASC11 interacts with hnRNP-K and activates the WNT/β-catenin pathway to promote growth and metastasis in colorectal cancer. Cancer Lett. 2016; 376(1):62-73. DOI: 10.1016/j.canlet.2016.03.022. View

15.

Dinicola S, Fabrizi G, Masiello M, Proietti S, Palombo A, Minini M . Inositol induces mesenchymal-epithelial reversion in breast cancer cells through cytoskeleton rearrangement. Exp Cell Res. 2016; 345(1):37-50. DOI: 10.1016/j.yexcr.2016.05.007. View

16.

Kazazian K, Go C, Wu H, Brashavitskaya O, Xu R, Dennis J . Plk4 Promotes Cancer Invasion and Metastasis through Arp2/3 Complex Regulation of the Actin Cytoskeleton. Cancer Res. 2016; 77(2):434-447. DOI: 10.1158/0008-5472.CAN-16-2060. View

17.

Liu Y, Wang Z, Huang D, Wu C, Li H, Zhang X . LMO2 promotes tumor cell invasion and metastasis in basal-type breast cancer by altering actin cytoskeleton remodeling. Oncotarget. 2016; 8(6):9513-9524. PMC: 5354749. DOI: 10.18632/oncotarget.13434. View

18.

Chan C, Pan Y, Nyberg K, Marra M, Lim E, Jones S . Tumour-suppressor microRNAs regulate ovarian cancer cell physical properties and invasive behaviour. Open Biol. 2016; 6(11). PMC: 5133448. DOI: 10.1098/rsob.160275. View

19.

Siegel R, Miller K, Jemal A . Cancer Statistics, 2017. CA Cancer J Clin. 2017; 67(1):7-30. DOI: 10.3322/caac.21387. View

20.

Huang D, Cao L, Zheng S . CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma. J Exp Clin Cancer Res. 2017; 36(1):13. PMC: 5240199. DOI: 10.1186/s13046-016-0474-0. View