Knockdown of LI-cadherin alters expression of matrix metalloproteinase-2 and -9 and galectin-3

Yu,Qiongfang; Shen,Wei; Zhou,Huangyan; Dong,Weiguo; Gao,Dian

doi:10.3892/mmr.2016.5069

Knockdown of LI-cadherin alters expression of matrix metalloproteinase-2 and -9 and galectin-3

Authors:
- Qiongfang Yu
- Wei Shen
- Huangyan Zhou
- Weiguo Dong
- Dian Gao
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Affiliations: Department of Gastroenterology and Hepatology, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Gastrointestinal Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Pathogen Biology and Immunology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Gastroenterology and Hepatology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Published online on: March 30, 2016 https://doi.org/10.3892/mmr.2016.5069
Pages: 4469-4474

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Abstract

Liver-intestine cadherin (LI-cadherin), a novel member of the cadherin family, has been associated with the ability of a tumor to acquire an aggressive phenotype in several types of cancer. However, the exact function of LI-cadherin in the process of tumor invasion and metastasis remains predominantly unknown. To explore the effect of LI-cadherin on the regulation of matrix metalloproteinase-2 (MMP-2), MMP-9 and galectin-3 in LoVo human colorectal cancer cells, a RNA interference technique was applied to suppress the expression of LI‑cadherin. Subsequently, the mRNA levels and activities of MMP-2 and -9 were analyzed by semi-quantitative reverse transcription-polymerase chain reaction and gelatin zymography, respectively. Additionally, the protein expression level of galectin-3 was determined by western blot analysis. The results of the present study demonstrated that short hairpin RNA (shRNA)-silencing of LI-cadherin significantly increased the mRNA levels and activities of MMP‑2 and ‑9, and significantly reduced the protein levels of galectin‑3 in LoVo cells compared with control shRNA (P<0.05). These data indicate that knockdown of LI‑cadherin facilitates the invasion of cancer cells by degrading extracellular matrix components via activation of MMP‑2 and ‑9, and increases cancer cell adhesion and migration via altered expression of galectin‑3. This suggests that LI‑cadherin serves an important role in the invasion and metastasis of colorectal cancer, and may be used as a potential therapeutic target.

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1	Bulgakova NA, Klapholz B and Brown NH: Cell adhesion in Drosophila: Versatility of cadherin and integrin complexes during development. Curr Opin Cell Biol. 24:702–712. 2012. View Article : Google Scholar : PubMed/NCBI
2	Leckband D and Sivasankar S: Cadherin recognition and adhesion. Curr Opin Cell Biol. 24:620–627. 2012. View Article : Google Scholar : PubMed/NCBI
3	Yan X, Yan L, Liu S, Shan Z, Tian Y and Jin Z: N-cadherin, a novel prognostic biomarker, drives malignant progression of colorectal cancer. Mol Med Rep. 12:2999–3006. 2015.PubMed/NCBI
4	Shapiro L and Weis WI: Structure and biochemistry of cadherins and catenins. Cold Spring Harb Perspect Biol. 1:a0030532009. View Article : Google Scholar :
5	van Roy F: Beyond E-cadherin: Roles of other cadherin superfamily members in cancer. Nat Rev Cancer. 14:121–134. 2014. View Article : Google Scholar : PubMed/NCBI
6	Takamura M, Yamagiwa S, Matsuda Y, Ichida T and Aoyagi Y: Involvement of liver-intestine cadherin in cancer progression. Med Mol Morphol. 46:1–7. 2013. View Article : Google Scholar : PubMed/NCBI
7	Bartolomé RA, Barderas R, Torres S, Fernandez-Aceñero MJ, Mendes M, García-Foncillas J, Lopez-Lucendo M and Casal JI: Cadherin-17 interacts with α2β1 integrin to regulate cell proliferation and adhesion in colorectal cancer cells causing liver metastasis. Oncogene. 33:1658–1669. 2014. View Article : Google Scholar
8	Su MC, Yuan RH, Lin CY and Jeng YM: Cadherin-17 is a useful diagnostic marker for adenocarcinomas of the digestive system. Mod Pathol. 21:1379–1386. 2008. View Article : Google Scholar : PubMed/NCBI
9	Berndorff D, Gessner R, Kreft B, Schnoy N, Lajous-Petter AM, Loch N, Reutter W, Hortsch M and Tauber R: Liver-intestine cadherin: Molecular cloning and characterization of a novel Ca(2+)-dependent cell adhesion molecule expressed in liver and intestine. J Cell Biol. 125:1353–1369. 1994. View Article : Google Scholar : PubMed/NCBI
10	Kreft B, Berndorff D, Böttinger A, Finnemann S, Wedlich D, Hortsch M, Tauber R and Gessner R: LI-cadherin-mediated cell-cell adhesion does not require cytoplasmic interactions. J Cell Biol. 136:1109–1121. 1997. View Article : Google Scholar : PubMed/NCBI
11	Takamura M, Ichida T, Matsuda Y, Kobayashi M, Yamagiwa S, Genda T, Shioji K, Hashimoto S, Nomoto M, Hatakeyama K, et al: Reduced expression of liver-intestine cadherin is associated with progression and lymph node metastasis of human colorectal carcinoma. Cancer Lett. 212:253–259. 2004. View Article : Google Scholar : PubMed/NCBI
12	Sakamoto N, Oue N, Sentani K, Anami K, Uraoka N, Naito Y, Oo HZ, Hinoi T, Ohdan H, Yanagihara K, et al: Liver-intestine cadherin induction by epidermal growth factor receptor is associated with intestinal differentiation of gastric cancer. Cancer Sci. 103:1744–1750. 2012. View Article : Google Scholar : PubMed/NCBI
13	Liu QS, Zhang J, Liu M and Dong WG: Lentiviral-mediated miRNA against liver-intestine cadherin suppresses tumor growth and invasiveness of human gastric cancer. Cancer Sci. 101:1807–1812. 2010. View Article : Google Scholar : PubMed/NCBI
14	Dong WG, Yu QF, Xu Y and Fan LF: Li-cadherin is inversely correlated with galectin-3 expression in gastric cancer. Dig Dis Sci. 53:1811–1817. 2008. View Article : Google Scholar
15	Park SS, Kang SH, Park JM, Kim JH, Oh SC, Lee JH, Chae YS, Kim SJ, Kim CS and Mok YJ: Expression of liver-intestine cadherin and its correlation with lymph node metastasis in gastric cancer: Can it predict N stage preoperatively? Ann Surg Oncol. 14:94–99. 2007. View Article : Google Scholar
16	Dong W, Yu Q and Xu Y: Altered expression of a Li-cadherin in gastric cancer and intestinal metaplasia. Dig Dis Sci. 52:536–542. 2007. View Article : Google Scholar : PubMed/NCBI
17	Takamura M, Sakamoto M, Ino Y, Shimamura T, Ichida T, Asakura H and Hirohashi S: Expression of liver-intestine cadherin and its possible interaction with galectin-3 in ductal adenocarcinoma of the pancreas. Cancer Sci. 94:425–430. 2003. View Article : Google Scholar : PubMed/NCBI
18	Fan ZJ, Fang XJ, Wang JX, Xue JF and Zhang Y: Expression of liver-intestine cadherin and its significance in hepatocellular carcinoma. Zhonghua Yi Xue Za Zhi. 91:2546–2548. 2011.In Chinese.
19	Ding ZB, Shi YH, Zhou J, Shi GM, Ke AW, Qiu SJ, Wang XY, Dai Z, Xu Y and Fan J: Liver-intestine cadherin predicts microvascular invasion and poor prognosis of hepatitis B virus-positive hepatocellular carcinoma. Cancer. 115:4753–4765. 2009. View Article : Google Scholar : PubMed/NCBI
20	Chen XT, Du HY, Yuan SF, Wang SM and Li M: Effect of monoclonal antibodies against LI-cadherin on the proliferation of human hepatocellular carcinoma cells. Nan Fang Yi Ke Da Xue Xue Bao. 29:880–883. 2009.In Chinese. PubMed/NCBI
21	Wang XQ, Luk JM, Garcia-Barcelo M, Miao X, Leung PP, Ho DW, Cheung ST, Lam BY, Cheung CK, Wong AS, et al: Liver intestine-cadherin (CDH17) haplotype is associated with increased risk of hepatocellular carcinoma. Clin Cancer Res. 12:5248–5252. 2006. View Article : Google Scholar : PubMed/NCBI
22	Wang XQ, Luk JM, Leung PP, Wong BW, Stanbridge EJ and Fan ST: Alternative mRNA splicing of liver intestine-cadherin in hepatocellular carcinoma. Clin Cancer Res. 11:483–489. 2005.PubMed/NCBI
23	Wong BW, Luk JM, Ng IO, Hu MY, Liu KD and Fan ST: Identification of liver-intestine cadherin in hepatocellular carcinoma - a potential disease marker. Biochem Biophys Res Commun. 311:618–624. 2003. View Article : Google Scholar : PubMed/NCBI
24	Ryu KH, Shim KN, Jung SA, Yoo K, Joo YH and Lee JH: Significance of preoperative tissue levels of vascular-endothelial cadherin, liver-intestine cadherin and vascular endothelial growth factor in gastric cancer. Korean J Gastroenterol. 60:229–241. 2012. View Article : Google Scholar : PubMed/NCBI
25	Ko S, Chu KM, Luk JM, Wong BW, Yuen ST, Leung SY and Wong J: Overexpression of LI-cadherin in gastric cancer is associated with lymph node metastasis. Biochem Biophys Res Commun. 319:562–568. 2004. View Article : Google Scholar : PubMed/NCBI
26	Fortuna-Costa A, Gomes AM, Kozlowski EO, Stelling MP and Pavão MS: Extracellular galectin-3 in tumor progression and metastasis. Front Oncol. 4:1382014. View Article : Google Scholar : PubMed/NCBI
27	Boscher C, Zheng YZ, Lakshminarayan R, Johannes L, Dennis JW, Foster LJ and Nabi IR: Galectin-3 protein regulates mobility of N-cadherin and GM1 ganglioside at cell-cell junctions of mammary carcinoma cells. J Biol Chem. 287:32940–32952. 2012. View Article : Google Scholar : PubMed/NCBI
28	Ochieng J, Fridman R, Nangia-Makker P, Kleiner DE, Liotta LA, Stetler-Stevenson WG and Raz A: Galectin-3 is a novel substrate for human matrix metalloproteinases-2 and -9. Biochemistry. 33:14109–14114. 1994. View Article : Google Scholar : PubMed/NCBI
29	Yu QF, Dong WG and Ren JL: Knockdown of Li-cadherin increases metastatic behaviors of LoVo cells. J Cancer Res Clin Oncol. 136:1641–1649. 2010. View Article : Google Scholar : PubMed/NCBI
30	Hadler-Olsen E, Winberg JO and Uhlin-Hansen L: Matrix metalloproteinases in cancer: Their value as diagnostic and prognostic markers and therapeutic targets. Tumour Biol. 34:2041–2051. 2013. View Article : Google Scholar : PubMed/NCBI
31	Brooks PC, Strömblad S, Sanders LC, von Schalscha TL, Aimes RT, Stetler-Stevenson WG, Quigley JP and Cheresh DA: Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3. Cell. 85:683–693. 1996. View Article : Google Scholar : PubMed/NCBI
32	Rolli M, Fransvea E, Pilch J, Saven A and Felding-Habermann B: Activated integrin alphavbeta3 cooperates with metalloproteinase MMP-9 in regulating migration of metastatic breast cancer cells. Proc Natl Acad Sci USA. 100:9482–9487. 2003. View Article : Google Scholar : PubMed/NCBI
33	Ochieng J, Green B, Evans S, James O and Warfield P: Modulation of the biological functions of galectin-3 by matrix metalloproteinases. Biochim Biophys Acta. 1379:97–106. 1998. View Article : Google Scholar : PubMed/NCBI
34	Song L, Tang JW, Owusu L, Sun M-Z, Wu J and Zhang J: Galectin-3 in cancer. Clin Chim Acta. 431:185–191. 2014. View Article : Google Scholar : PubMed/NCBI
35	Kwak JM, Min BW, Lee JH, Choi JS, Lee SI, Park SS, Kim J, Um JW, Kim SH and Moon HY: The prognostic significance of E-cadherin and liver intestine-cadherin expression in colorectal cancer. Dis Colon Rectum. 50:1873–1880. 2007. View Article : Google Scholar : PubMed/NCBI
36	Baumgartner W: Possible roles of LI-Cadherin in the formation and maintenance of the intestinal epithelial barrier. Tissue Barriers. 1:e238152013. View Article : Google Scholar : PubMed/NCBI