Loss of Cell Adhesion Molecule L1 Like Promotes Tumor Growth and Metastasis in Esophageal Squamous Cell Carcinoma

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2019 Jan 10

PMID 30622339

Citations 17

Authors

Hong Tang

Lingxi Jiang

Cailei Zhu

Raymond Liu

Yufeng Wu

Qian Yan

Ming Liu

Yongxu Jia

Juan Chen

Yanru Qin

Victor Ho-Fun Lee

Suxia Luo

Qiming Wang

Xin-Yuan Guan

Affiliations

Soon will be listed here.

Abstract

Esophageal squamous cells carcinoma (ESCC) is a major common thoracic tumor characterized by distinctly high incidences and mortality rates. Despite advances in multimodality therapy, the mortality rate of ESCC remains high and understanding of molecular alterations leading to the development and progression of ESCC is still very limited. In this study, a new tumor suppressor candidate, cell adhesion molecule with homology to L1CAM (CHL1), located at 3p26 which was frequently deleted in ESCC was identified. Reduced expression of CHL1 correlated with poor differentiation, increased invasion, and lymph-node metastasis, advanced tumor stage, and decreased overall survival. Methylation-specific PCR and FISH assays revealed that down-regulation of CHL1 in both ESCC cell lines and clinical samples were associated with promoter hypermethylation and loss of heterozygosity. Functional studies using lentiviral-based overexpression and knockdown systems provided direct support of CHL1 to function as an important tumor suppressor with both anti-proliferation and anti-metastasis abilities, through Merlin and SEMA3B-Np1-mediated inhibition of AKT signaling pathway. Further characterization of CHL1 may provide a novel therapeutic target in ESCC treatment.

Citing Articles

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References

Dalbagni G, Presti J, Reuter V, Fair W, Cordon-Cardo C . Genetic alterations in bladder cancer. Lancet. 1993; 342(8869):469-71. DOI: 10.1016/0140-6736(93)91595-d. View

Fu L, Qin Y, Xie D, Hu L, Kwong D, Srivastava G . Characterization of a novel tumor-suppressor gene PLC delta 1 at 3p22 in esophageal squamous cell carcinoma. Cancer Res. 2007; 67(22):10720-6. DOI: 10.1158/0008-5472.CAN-07-2411. View

Wright A, Demyanenko G, Powell A, Schachner M, Enriquez-Barreto L, Tran T . Close homolog of L1 and neuropilin 1 mediate guidance of thalamocortical axons at the ventral telencephalon. J Neurosci. 2007; 27(50):13667-79. PMC: 6673613. DOI: 10.1523/JNEUROSCI.2888-07.2007. View

Tao Q, Huang H, Geiman T, Lim C, Fu L, Qiu G . Defective de novo methylation of viral and cellular DNA sequences in ICF syndrome cells. Hum Mol Genet. 2002; 11(18):2091-102. DOI: 10.1093/hmg/11.18.2091. View

Yamaguchi H, Condeelis J . Regulation of the actin cytoskeleton in cancer cell migration and invasion. Biochim Biophys Acta. 2006; 1773(5):642-52. PMC: 4266238. DOI: 10.1016/j.bbamcr.2006.07.001. View

Ke L . Mortality and incidence trends from esophagus cancer in selected geographic areas of China circa 1970-90. Int J Cancer. 2002; 102(3):271-4. DOI: 10.1002/ijc.10706. View

Zhu C, Qin Y, Xie D, Chua D, Fung J, Chen L . Characterization of tumor suppressive function of P300/CBP-associated factor at frequently deleted region 3p24 in esophageal squamous cell carcinoma. Oncogene. 2009; 28(31):2821-8. DOI: 10.1038/onc.2009.137. View

Castro-Rivera E, Ran S, Brekken R, Minna J . Semaphorin 3B inhibits the phosphatidylinositol 3-kinase/Akt pathway through neuropilin-1 in lung and breast cancer cells. Cancer Res. 2008; 68(20):8295-303. PMC: 2760388. DOI: 10.1158/0008-5472.CAN-07-6601. View

Knosel T, Schluns K, Dietel M, Petersen I . Chromosomal alterations in lung metastases of colorectal carcinomas: associations with tissue specific tumor dissemination. Clin Exp Metastasis. 2006; 22(7):533-8. DOI: 10.1007/s10585-005-5239-7. View

10.

Xie D, Sham J, Zeng W, Lin H, Che L, Wu H . Heterogeneous expression and association of beta-catenin, p16 and c-myc in multistage colorectal tumorigenesis and progression detected by tissue microarray. Int J Cancer. 2003; 107(6):896-902. DOI: 10.1002/ijc.11514. View

11.

Schlatter M, Buhusi M, Wright A, Maness P . CHL1 promotes Sema3A-induced growth cone collapse and neurite elaboration through a motif required for recruitment of ERM proteins to the plasma membrane. J Neurochem. 2007; 104(3):731-44. DOI: 10.1111/j.1471-4159.2007.05013.x. View

12.

Ogasawara S, Maesawa C, Tamura G, SATODATE R . Frequent microsatellite alterations on chromosome 3p in esophageal squamous cell carcinoma. Cancer Res. 1995; 55(4):891-4. View

13.

Chen J, Fu L, Zhang L, Kwong D, Yan L, Guan X . Tumor suppressor genes on frequently deleted chromosome 3p in nasopharyngeal carcinoma. Chin J Cancer. 2012; 31(5):215-22. PMC: 3777521. DOI: 10.5732/cjc.011.10364. View

14.

Presti Jr J, Reuter V, Galan T, Fair W, Cordon-Cardo C . Molecular genetic alterations in superficial and locally advanced human bladder cancer. Cancer Res. 1991; 51(19):5405-9. View

15.

Qin Y, Fu L, Sham P, Kwong D, Zhu C, Chu K . Single-nucleotide polymorphism-mass array reveals commonly deleted regions at 3p22 and 3p14.2 associate with poor clinical outcome in esophageal squamous cell carcinoma. Int J Cancer. 2008; 123(4):826-30. DOI: 10.1002/ijc.23577. View

16.

Kwong D, Lam A, Guan X, Law S, Tai A, Wong J . Chromosomal aberrations in esophageal squamous cell carcinoma among Chinese: gain of 12p predicts poor prognosis after surgery. Hum Pathol. 2004; 35(3):309-16. DOI: 10.1016/j.humpath.2003.10.020. View

17.

Raju S, Hauff S, Lemieux A, Orosco R, Gross A, Nguyen L . Combined TP53 mutation/3p loss correlates with decreased radiosensitivity and increased matrix-metalloproteinase activity in head and neck carcinoma. Oral Oncol. 2015; 51(5):470-5. PMC: 4427339. DOI: 10.1016/j.oraloncology.2015.01.014. View

18.

Ognibene M, Pagnan G, Marimpietri D, Cangelosi D, Cilli M, Benedetti M . gene acts as a tumor suppressor in human neuroblastoma. Oncotarget. 2018; 9(40):25903-25921. PMC: 5995240. DOI: 10.18632/oncotarget.25403. View

19.

Portale G, Hagen J, Peters J, Chan L, DeMeester S, Gandamihardja T . Modern 5-year survival of resectable esophageal adenocarcinoma: single institution experience with 263 patients. J Am Coll Surg. 2006; 202(4):588-96. DOI: 10.1016/j.jamcollsurg.2005.12.022. View

20.

Qian C, Berghuis B, Tsarfaty G, Bruch M, Kort E, Ditlev J . Preparing the "soil": the primary tumor induces vasculature reorganization in the sentinel lymph node before the arrival of metastatic cancer cells. Cancer Res. 2006; 66(21):10365-76. DOI: 10.1158/0008-5472.CAN-06-2977. View