Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Tumor Biology
Published in: Tumor Biology 3/2016

01-03-2016 | Original Article

CCL18/PITPNM3 enhances migration, invasion, and EMT through the NF-κB signaling pathway in hepatocellular carcinoma

Authors: Zeyu Lin, Wenbin Li, Heyun Zhang, Wei Wu, Yaorong Peng, Yunjie Zeng, Yunle Wan, Jie Wang, Nengtai Ouyang

Published in: Tumor Biology | Issue 3/2016

Login to get access

Abstract

Chemokine ligand 18 (CCL18) has been associated with hepatocellular carcinoma (HCC) metastasis. Here, we demonstrated a novel mechanism through which CCL18 enhances cell migration, invasion, and epithelial–mesenchymal transition (EMT) in HCC. (1) Using immunohistochemistry, we analyzed the expression of PITPNM3, a molecule that correlated with CCL18 signaling, in 149 HCC tissue specimens. The results showed that PITPNM3 expression is highly associated with tumor metastasis and differentiation; (2) in vitro experiments showed that CCL18 enhances cell migration, invasion, and EMT in PITPNM3(+) HCC cells but not in PITPNM3(-) cells. Silencing of PITPNM3 by short interfering RNA (siRNA) inhibited the induction of cell migration, invasion, and EMT by CCL18; (3) Cell migration, invasion, and EMT induced by CCL18 accompanied with the phosphorylation of IKK and IKBα as well as p65 nuclear translocation in PITPNM3(+) HCC cells, but not in the cells that PITPNM3 is silenced with siRNA, implying that the activation of NF-κB signaling is involved in the action of CCL18/PITPNM3. These results suggest that CCL18 enhances HCC cell migration, invasion, and EMT through the expression of PITPNM3 and the activation of the NF-κB signaling pathway.
Literature
1.
2.
3.
4.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed
5.
Bridges JF, Joy SM, Gallego G, Kudo M, Ye SL, Han KH, et al. Needs for hepatocellular carcinoma control policy in the Asia-Pacific region. Asian Pac J Cancer Prev. 2011;12:2585–91.PubMed
6.
7.
8.
Zhou SL, Zhou ZJ, Hu ZQ, Li X, Huang XW, Wang Z, et al. Cxcr2/cxcl5 axis contributes to epithelial-mesenchymal transition of hcc cells through activating pi3k/akt/gsk-3beta/Snail signaling. Cancer Lett. 2015;358:124–35.CrossRefPubMed
9.
Gao Y, Ruan B, Liu W, Wang J, Yang X, Zhang Z, et al. Knockdown of cd44 inhibits the invasion and metastasis of hepatocellular carcinoma both in vitro and in vivo by reversing epithelial–mesenchymal transition. Oncotarget. 2015.
10.
Li L, Li W. Epithelial–mesenchymal transition in human cancer: comprehensive reprogramming of metabolism, epigenetics, and differentiation. Pharmacol Ther. 2015.
11.
Song R, Song H, Liang Y, Yin D, Zhang H, Zheng T, et al. Reciprocal activation between atpase inhibitory factor 1 and nf-kappab drives hepatocellular carcinoma angiogenesis and metastasis. Hepatology. 2014;60:1659–73.CrossRefPubMed
12.
Huang RY, Guilford P, Thiery JP. Early events in cell adhesion and polarity during epithelial–mesenchymal transition. J Cell Sci. 2012;125:4417–22.CrossRefPubMed
13.
Yang JD, Nakamura I, Roberts LR. The tumor microenvironment in hepatocellular carcinoma: current status and therapeutic targets. Semin Cancer Biol. 2011;21:35–43.CrossRefPubMed
14.
Hernandez-Gea V, Toffanin S, Friedman SL, Llovet JM. Role of the microenvironment in the pathogenesis and treatment of hepatocellular carcinoma. Gastroenterology. 2013;144:512–27.CrossRefPubMedPubMedCentral
15.
Calon A, Espinet E, Palomo-Ponce S, Tauriello DV, Iglesias M, Cespedes MV, et al. Dependency of colorectal cancer on a tgf-beta-driven program in stromal cells for metastasis initiation. Cancer Cell. 2012;22:571–84.CrossRefPubMedPubMedCentral
16.
Goetz JG, Minguet S, Navarro-Lerida I, Lazcano JJ, Samaniego R, Calvo E, et al. Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis. Cell. 2011;146:148–63.CrossRefPubMedPubMedCentral
17.
Luker KE, Lewin SA, Mihalko LA, Schmidt BT, Winkler JS, Coggins NL, et al. Scavenging of cxcl12 by cxcr7 promotes tumor growth and metastasis of cxcr4-positive breast cancer cells. Oncogene. 2012;31:4750–8.CrossRefPubMedPubMedCentral
18.
19.
20.
Chen J, Yao Y, Gong C, Yu F, Su S, Liu B, et al. Ccl18 from tumor-associated macrophages promotes breast cancer metastasis via pitpnm3. Cancer Cell. 2011;19:541–55.CrossRefPubMedPubMedCentral
21.
Su S, Liu Q, Chen J, Chen F, He C, Huang D, et al. A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis. Cancer Cell. 2014;25:605–20.CrossRefPubMed
22.
Wan S, Zhao E, Kryczek I, Vatan L, Sadovskaya A, Ludema G, et al. Tumor-associated macrophages produce interleukin 6 and signal via stat3 to promote expansion of human hepatocellular carcinoma stem cells. Gastroenterology. 2014;147:1393–404.CrossRefPubMedPubMedCentral
23.
Condeelis J, Pollard JW. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell. 2006;124:263–6.CrossRefPubMed
24.
25.
He C, Su S, Chen F, Huang D, Zheng F, Huang W, et al. Overexpression of pitpnm3 promotes hepatocellular carcinoma cell metastasis. Chin Sci Bull. 2014;59:1326–33.CrossRef
26.
Theiss AL. Sphingosine-1-phosphate: driver of nfkappab and stat3 persistent activation in chronic intestinal inflammation and colitis-associated cancer. JAKSTAT. 2013;2, e24150.PubMedPubMedCentral
27.
Pal S, Bhattacharjee A, Ali A, Mandal NC, Mandal SC, Pal M. Chronic inflammation and cancer: potential chemoprevention through nuclear factor kappa b and p53 mutual antagonism. J Inflamm (Lond). 2014;11:23.CrossRef
28.
Karin M, Greten FR. Nf-κb: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol. 2005;5:749–59.CrossRefPubMed
29.
30.
Martinez FO, Helming L, Gordon S. Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol. 2009;27:451–83.CrossRefPubMed
31.
Prasse A, Pechkovsky DV, Toews GB, Schafer M, Eggeling S, Ludwig C, et al. Ccl18 as an indicator of pulmonary fibrotic activity in idiopathic interstitial pneumonias and systemic sclerosis. Arthritis Rheum. 2007;56:1685–93.CrossRefPubMed
32.
Pochetuhen K, Luzina IG, Lockatell V, Choi J, Todd NW, Atamas SP. Complex regulation of pulmonary inflammation and fibrosis by ccl18. Am J Pathol. 2007;171:428–37.CrossRefPubMedPubMedCentral
33.
Chang CY, Lee YH, Leu SJ, Wang CY, Wei CP, Hung KS, et al. Cc-chemokine ligand 18/pulmonary activation-regulated chemokine expression in the cns with special reference to traumatic brain injuries and neoplastic disorders. Neuroscience. 2010;165:1233–43.CrossRefPubMed
34.
35.
Catusse J, Wollner S, Leick M, Schrottner P, Schraufstatter I, Burger M. Attenuation of cxcr4 responses by ccl18 in acute lymphocytic leukemia b cells. J Cell Physiol. 2010;225:792–800.CrossRefPubMed
36.
Zhu Y, Liu Y, Qian Y, Dai X, Yang L, Chen J, et al. Research on the efficacy of celastrus orbiculatus in suppressing tgf-beta1-induced epithelial-mesenchymal transition by inhibiting hsp27 and tnf-alpha-induced nf-kappa b/Snail signaling pathway in human gastric adenocarcinoma. BMC Complement Altern Med. 2014;14:433.CrossRefPubMedPubMedCentral
37.
Yang Y, Li Y, Wang K, Wang Y, Yin W, Li L. P38/nf-kappab/snail pathway is involved in caffeic acid-induced inhibition of cancer stem cells-like properties and migratory capacity in malignant human keratinocyte. PLoS One. 2013;8, e58915.CrossRefPubMedPubMedCentral
Metadata
Title
CCL18/PITPNM3 enhances migration, invasion, and EMT through the NF-κB signaling pathway in hepatocellular carcinoma
Authors
Zeyu Lin
Wenbin Li
Heyun Zhang
Wei Wu
Yaorong Peng
Yunjie Zeng
Yunle Wan
Jie Wang
Nengtai Ouyang
Publication date
01-03-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 3/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4172-x

Other articles of this Issue 3/2016

Tumor Biology 3/2016 Go to the issue

Original Article

XPC (A2920C), XPF (T30028C), TP53 (Arg72Pro), and GSTP1 (Ile105Val) polymorphisms in prognosis of cutaneous melanoma

Original Article

c-Myc-regulated long non-coding RNA H19 indicates a poor prognosis and affects cell proliferation in non-small-cell lung cancer

Original Article

MiR-30a regulates the proliferation, migration, and invasion of human osteosarcoma by targeting Runx2

Original Article

Ribonucleotide reductase large subunit M1 plays a different role in the invasion and metastasis of papillary thyroid carcinoma and undifferentiated thyroid carcinoma

Original Article

Expression of CDC5L is associated with tumor progression in gliomas

Original Article

PI-88 inhibits postoperative recurrence of hepatocellular carcinoma via disrupting the surge of heparanase after liver resection
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits