L1 is associated with micrometastatic spread and poor outcome in colorectal cancer

Metastasis and cell adhesion are key aspects of cancer progression. Neurofascin (NFASC) is a member of the immunoglobulin superfamily of adhesion molecules and, while studies on NFASC are inadequate, other members have been indicated pivotal roles in cancer progression and metastasis. This study aimed at increasing the knowledge on the involvement of adhesion molecules in lung cancer progression by studying the regulation and role of NFASC in non‐small cell lung cancer (NSCLC). Here, copy number variations in the NFASC gene were analyzed in tumor and non‐tumorous lung tissues of 204 NSCLC patients. Frequent gene amplifications (OR = 4.50, 95%CI: 2.27‐8.92, P ≤ 0.001) and increased expression of NFASC (P = 0.034) were identified in tumors of NSCLC patients. Furthermore, molecular mechanisms of NFASC in lung cancer progression were evaluated by investigating the effects of NFASC silencing on cell proliferation, viability, migration, and invasion using siRNA technology in four NSCLC cell lines. Silencing of NFASC did not affect cell proliferation or viability but rather decreased NSCLC cell migration (P ≤ 0.001) and led to morphological changes, rearrangements in the actin cytoskeleton and changes in F‐actin networks in migrating NSCLC cell lines. This study is the first to report frequent copy number gain and increased expression of NFASC in NSCLC. Moreover, these data suggest that NFASC is a novel regulator of NSCLC cell motility and support a role of NFASC in the regulation of NSCLC progression.

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“…However, copy number gain and increased expression of L1 have been demonstrated in breast cancer 36, 7, 8, 9, 10, 11…”

Section: Discussionmentioning

confidence: 99%

Copy number variation, increased gene expression, and molecular mechanisms of neurofascin in lung cancer

Erdem

Arnoldussen

Skaug

et al. 2017

Molecular Carcinogenesis

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“…Subsequent work has shown overexpression of L1CAM in a variety of human tumours, in which it is associated with bad prognosis and metastases formation (Thies et al, 2002;Fogel et al, 2003a, b;Boo et al, 2007;Kaifi et al, 2007). Furthermore, L1CAM was detected in tumour-associated endothelium (Issa et al, 2009;Maddaluno et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

L1CAM–integrin interaction induces constitutive NF-κB activation in pancreatic adenocarcinoma cells by enhancing IL-1β expression

et al. 2010

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L1 cell adhesion molecule (L1CAM) overexpression is often associated with bad prognosis in various human carcinomas. Recent studies also suggest a role of L1CAM in pancreatic ductal adenocarcinomas (PDAC). To further address its contribution, we expressed functional domains of L1CAM in PT45-P1 PDAC cells. We found that L1CAM that is full length (L1-FL), but neither the soluble ectodomain (L1ecto) nor the cytoplasmic part (L1cyt), could enhance cell proliferation or tumour growth in mice. Expression of L1-FL resulted in constitutive activation of NF-jB, which was abolished by L1CAM knockdown. We showed that the expression of IL-1b was selectively upregulated by L1-FL, and increased IL-1b levels were instrumental for sustained NF-jB activation. IL-1b production and NF-jB activation were abolished by knockdown of a5-integrin and integrin-linked kinase, but insensitive to depletion of L1CAM cleavage proteinases. Supporting these data, PT45-P1 cells transduced with an L1CAM mutant deficient in integrin binding (L1-RGE) did not support the described L1-FL functions. Our results suggest that membranous L1CAM interacts with RGD-binding integrins, leading to sustained NF-jB activation by IL-1b production and autocrine/paracrine signalling. The unravelling of this novel mechanism sheds new light on the important role of L1CAM expression in PDAC cells.

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“…Expression is often found at the invasive front of primary tumors [24], strongly supporting a role for L1CAM in metastasis. Increased expression of L1CAM has been correlated with lymph node metastases, advanced tumor stage and reduced patient survival [24,25]. In our material CD171 expression was more prominent in borderline and malignant tumors than benign cystadenomas, but it did not relate to tumor grade or stage of the disease.…”

Section: Discussionmentioning

confidence: 61%

The immunohistochemical expression of CD24 and CD171 adhesion molecules in borderline ovarian tumors

Moulla¹,

Miliaras²,

Sioga³

et al. 2013

pjp

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CD24 and CD171 are cell adhesion proteins, which have been shown to be overexpressed in several carcinomas and to be associated with a poor clinical outcome. Our aim was to determine the expression of these two adhesion molecules in ovarian borderline neoplasms. We investigated 50 ovarian borderline tumors (serous, mucinous and endometrioid) as well as 29 benign cystadenomas and 25 carcinomas, which were used as controls. Paraffin sections were stained immunohistochemically for CD24 and CD171, and their expression was recorded in a semi-quantitative manner. In normal epithelium and benign ovarian cystadenomas both the CD24 and CD171 expression was negative to low, while their expression was significantly increased in borderline and malignant ovarian tumors. High-grade carcinomas, and carcinomas with metastases to the omentum presented considerably higher CD24 expression than low-grade carcinomas, and carcinomas without metastases. In addition, a few borderline and many malignant tumors presented cytoplasmic CD24 immunoreactivity, whereas all benign and most borderline tumors showed apical localization of this molecule. In conclusion, borderline tumors and carcinomas of the ovary present increased expression of CD24 and CD171 in relation to their benign counterparts, as is the case in malignant tumors of other organs. Change of staining pattern of CD24 (apical to cytoplasmic) apparently relates to a more aggressive phenotype.

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L1 is associated with micrometastatic spread and poor outcome in colorectal cancer

Cited by 73 publications

References 38 publications

Copy number variation, increased gene expression, and molecular mechanisms of neurofascin in lung cancer

Copy number variation, increased gene expression, and molecular mechanisms of neurofascin in lung cancer

L1CAM–integrin interaction induces constitutive NF-κB activation in pancreatic adenocarcinoma cells by enhancing IL-1β expression

The immunohistochemical expression of CD24 and CD171 adhesion molecules in borderline ovarian tumors

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