Pin2/TRF1‑binding protein X1 inhibits colorectal cancer cell migration and invasion in vitro and metastasis in vivo via the nuclear factor‑κB signaling pathway Retraction in /10.3892/or.2023.8477

Jiang,Tao; Li,Haiqing; Jiang,Ranran; Li,Hailong; Hou,Pingfu; Chen,Yansu; Bai,Jin; Song,Jun

doi:10.3892/or.2018.6570

Pin2/TRF1‑binding protein X1 inhibits colorectal cancer cell migration and invasion in vitro and metastasis in vivo via the nuclear factor‑κB signaling pathway

Retraction in: /10.3892/or.2023.8477

Authors:
- Tao Jiang
- Haiqing Li
- Ranran Jiang
- Hailong Li
- Pingfu Hou
- Yansu Chen
- Jin Bai
- Jun Song
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Affiliations: Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China, School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China
Published online on: July 13, 2018 https://doi.org/10.3892/or.2018.6570
Pages: 1533-1544

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Abstract

Pin2/TRF1‑binding protein X1 (PinX1) functioned as a potent inhibitor of telomerase, which was also widely considered to be a sufficient tumor suppressor. Previous studies have demonstrated that PinX1 expression was reduced in several types of cancer and was associated with poor overall survival. However, little is known regarding the role of PinX1 in colorectal cancer (CRC). The present study investigated PinX1 expression via immunostaining of CRC tissue microarrays consisting of tumor and adjacent non‑cancerous tissues (ANCT) from 568 patients. PinX1 expression was significantly lower in CRC tissues than in ANCT. Decreased PinX1 expression was revealed to be associated with lymph node metastasis, distant metastasis and advanced Tumor‑Node‑Metastasis stage, as well as a poorer overall and disease‑free survival. Furthermore, Cox regression analysis determined that a decreased PinX1 expression was an independent prognostic marker for patients with CRC. In an in vitro assay, PinX1 markedly restricted CRC cell migration and invasion. Additionally, the present study revealed that PinX1 could hinder the activity of matrix metalloproteinase 2 (MMP2) through nuclear factor (NF)‑κB‑dependent transcription to further suppress the migration and invasion ability of CRC cells through western blot analysis and a gelatin zymography assay. In vivo studies verified that PinX1 could suppress CRC metastasis, as well as the expression of MMP2 and NF‑κB p65. These results suggested that PinX1 can serve as an independent prognostic factor for patients with CRC and that it may function as a tumor metastasis suppressor in the progression of CRC though negatively regulating the NF‑κB/MMP2 signaling pathway.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI
2	Siegel R, Desantis C and Jemal A: Colorectal cancer statistics, 2014. CA Cancer J Clin. 64:104–117. 2014. View Article : Google Scholar : PubMed/NCBI
3	Becker SA, Zhou YZ and Slagle BL: Frequent loss of chromosome 8p in hepatitis B virus-positive hepatocellular carcinomas from China. Cancer Res. 56:5092–5097. 1996.PubMed/NCBI
4	Baffa R, Santoro R, Bullrich F, Mandes B, Ishii H and Croce CM: Definition and refinement of chromosome 8p regions of loss of heterozygosity in gastric cancer. Clin Cancer Res. 6:1372–1377. 2000.PubMed/NCBI
5	Johnson FB: PinX1 the tail on the chromosome. J Clin Invest. 121:1242–1244. 2011. View Article : Google Scholar : PubMed/NCBI
6	Zhou XZ and Lu KP: The Pin2/TRF1-interacting protein PinX1 is a potent telomerase inhibitor. Cell. 107:347–359. 2001. View Article : Google Scholar : PubMed/NCBI
7	Kondo T, Oue N, Mitani Y, Kuniyasu H, Noguchi T, Kuraoka K, Nakayama H and Yasui W: Loss of heterozygosity and histone hypoacetylation of the PINX1 gene are associated with reduced expression in gastric carcinoma. Oncogene. 24:157–164. 2005. View Article : Google Scholar : PubMed/NCBI
8	Kim MS, Kim SS, Yoo NJ and Lee SH: Somatic mutation of PINX1 gene is rare in common solid cancers. APMIS. 120:770–771. 2012. View Article : Google Scholar : PubMed/NCBI
9	Ma Y, Wu L, Liu C, Xu L, Li D and Li JC: The correlation of genetic instability of PINX1 gene to clinico-pathological features of gastric cancer in the Chinese population. J Cancer Res Clin Oncol. 135:431–437. 2009. View Article : Google Scholar : PubMed/NCBI
10	Shi M, Cao M, Song J, Liu Q, Li H, Meng F, Pan Z, Bai J and Zheng J: PinX1 inhibits the invasion and metastasis of human breast cancer via suppressing NF-κB/MMP-9 signaling pathway. Mol Cancer. 14:662015. View Article : Google Scholar : PubMed/NCBI
11	Li HL, Han L, Chen HR, Meng F, Liu QH, Pan ZQ, Bai J and Zheng JN: PinX1 serves as a potential prognostic indicator for clear cell renal cell carcinoma and inhibits its invasion and metastasis by suppressing MMP-2 via NF-κB-dependent transcription. Oncotarget. 6:21406–21420. 2015.PubMed/NCBI
12	Cai MY, Zhang B, He WP, Yang GF, Rao HL, Rao ZY, Wu QL, Guan XY, Kung HF, Zeng YX, et al: Decreased expression of PinX1 protein is correlated with tumor development and is a new independent poor prognostic factor in ovarian carcinoma. Cancer Sci. 101:1543–1549. 2010. View Article : Google Scholar : PubMed/NCBI
13	Weiser MR: AJCC 8th Edition: Colorectal Cancer. Ann Surg Oncol. 25:1454–1455. 2018. View Article : Google Scholar : PubMed/NCBI
14	Yin LL, Chung CM, Chen J, Fok KL, Ng CP, Jia RR, Ren X, Zhou J, Zhang T, Zhao XH, et al: A suppressor of multiple extracellular matrix-degrading proteases and cancer metastasis. J Cell Mol Med. 13:4034–4041. 2009. View Article : Google Scholar : PubMed/NCBI
15	DeClerck YA, Mercurio AM, Stack MS, Chapman HA, Zutter MM, Muschel RJ, Raz A, Matrisian LM, Sloane BF, Noel A, et al: Proteases, extracellular matrix, and cancer: A workshop of the path B study section. Am J Pathol. 164:1131–1139. 2004. View Article : Google Scholar : PubMed/NCBI
16	Karin M, Cao Y, Greten FR and Li ZW: NF-κB in cancer: From innocent bystander to major culprit. Nat Rev Cancer. 2:301–310. 2002. View Article : Google Scholar : PubMed/NCBI
17	Wang W, Abbruzzese JL, Evans DB and Chiao PJ: Overexpression of urokinase-type plasminogen activator in pancreatic adenocarcinoma is regulated by constitutively activated RelA. Oncogene. 18:4554–4563. 1999. View Article : Google Scholar : PubMed/NCBI
18	Takeshita H, Yoshizaki T, Miller WE, Sato H, Furukawa M, Pagano JS and Raab-Traub N: Matrix metalloproteinase 9 expression is induced by Epstein-Barr virus latent membrane protein 1 C-terminal activation regions 1 and 2. J Virol. 73:5548–5555. 1999.PubMed/NCBI
19	Bond M, Fabunmi RP, Baker AH and Newby AC: Synergistic upregulation of metalloproteinase-9 by growth factors and inflammatory cytokines: An absolute requirement for transcription factor NF-kappa B. FEBS Lett. 435:29–34. 1998. View Article : Google Scholar : PubMed/NCBI
20	Duffy MJ: The biochemistry of metastasis. Adv Clin Chem. 32:135–166. 1996. View Article : Google Scholar : PubMed/NCBI
21	Price JT, Bonovich MT and Kohn EC: The biochemistry of cancer dissemination. Crit Rev Biochem Mol Biol. 32:175–253. 1997. View Article : Google Scholar : PubMed/NCBI
22	Xu X, Wang Y, Chen Z, Sternlicht MD, Hidalgo M and Steffensen B: Matrix metalloproteinase-2 contributes to cancer cell migration on collagen. Cancer Res. 65:130–136. 2005.PubMed/NCBI
23	Li HC, Cao DC, Liu Y, Hou YF, Wu J, Lu JS, Di GH, Liu G, Li FM, Ou ZL, et al: Prognostic value of matrix metalloproteinases (MMP-2 and MMP-9) in patients with lymph node-negative breast carcinoma. Breast Cancer Res Treat. 88:75–85. 2004. View Article : Google Scholar : PubMed/NCBI
24	Chu D, Zhao Z, Zhou Y, Li Y, Li J, Zheng J, Zhao Q and Wang W: Matrix metalloproteinase-9 is associated with relapse and prognosis of patients with colorectal cancer. Ann Surg Oncol. 19:318–325. 2012. View Article : Google Scholar : PubMed/NCBI
25	Langers AM, Verspaget HW, Hawinkels LJ, Kubben FJ, van Duijn W, van der Reijden JJ, Hardwick JC, Hommes DW and Sier CF: MMP-2 and MMP-9 in normal mucosa are independently associated with outcome of colorectal cancer patients. Br J Cancer. 106:1495–1498. 2012. View Article : Google Scholar : PubMed/NCBI
26	Brew K, Dinakarpandian D and Nagase H: Tissue inhibitors of metalloproteinases: Evolution, structure and function. Biochim Biophys Acta. 1477:267–283. 2000. View Article : Google Scholar : PubMed/NCBI
27	Lambert E, Dassé E, Haye B and Petitfrère E: TIMPs as multifacial proteins. Crit Rev Oncol Hematol. 49:187–198. 2004. View Article : Google Scholar : PubMed/NCBI
28	Ma J, Mi C, Wang KS, Lee JJ and Jin X: Zinc finger protein 91 (ZFP91) activates HIF-1α via NF-κB/p65 to promote proliferation and tumorigenesis of colon cancer. Oncotarget. 7:36551–36562. 2016.PubMed/NCBI
29	Lee WR, Chung CL, Hsiao CJ, Chou YC, Hsueh PJ, Yang PC, Jan JS, Cheng YW and Hsiao G: Suppression of matrix metalloproteinase-9 expression by andrographolide in human monocytic THP-1 cells via inhibition of NF-κB activation. Phytomedicine. 19:270–277. 2012. View Article : Google Scholar : PubMed/NCBI
30	Jianfeng D, Feng J, Chaoneng J, Zhongzhou Z, Shaohua G, Qihan W, Liu W, Gang Y, Yi X and Mao Y: Cloning of the correct full length cDNA of NF-kappaB-repressing factor. Mol Cells. 16:397–401. 2003.PubMed/NCBI
31	Nourbakhsh M and Hauser H: Constitutive silencing of IFN-beta promoter is mediated by NRF (NF-kappa B-repressing factor), a nuclear inhibitor of NF-kappa B. EMBO J. 18:6415–6425. 1999. View Article : Google Scholar : PubMed/NCBI