Id1 Promotes Tumor Cell Migration in Nonsmall Cell Lung Cancers

Abstract

Id1, which belongs to the Id family of helix-loop-helix transcription factors has been most associated with tumor progression and metastatsis; however, its significance in lung cancers has not been extensively explored. Here we seek to evaluate the expression of Id1 in a pilot study of nonsmall-cell lung cancers (NSCLCs) and determine its diagnostic and functional significance in these tumors. Paired normal and malignant lung tissues as well as a panel of NSCLC primary tumors and cell lines were evaluated for Id1 expression using Western blotting and quantitative RT-PCR. Functional assays were performed to evaluate the role of Id1 in tumor cell growth, migration and progression. We find Id1 expression is upregulated in squamous cell carcinoma when compared to adenocarcinoma of the lung and that expression of Id1 versus the normal control is variable in NSCLCs. We also note that Id1 expression in NSCLC cells is largely growth factor dependant and constitutive expression of Id1 in NSCLC cells significantly increases tumor cell migration without affecting cell proliferation. We conclude that Id1, as a mediator of tumor cell migration, may be an indicator of aggressive potential in nonsmall-cell lung cancers.

ID1 Facilitates the Growth and Metastasis of Non-Small Cell Lung Cancer in Response to Nicotinic Acetylcholine Receptor and Epidermal Growth Factor Receptor Signaling

“…The finding that both nicotine and EGF can induce the expression of ID1 in a Src-dependent manner raises the possibility that ID1 might be contributing to oncogenesis in smokers and nonsmokers. Our results showing that ID1 is involved in tumor cell migrations are in agreement with a recent study showing that ID1 promotes tumor cell migration in NSCLC (4). Several studies have shown that the decrease in E-cadherin and ␤-catenin with a concurrent increase in fibronectin and vimentin levels is one of the hallmarks of epithelial-mesenchymal transition in lung cancer cells (24).…”

“…Recently ID1 has been shown to be expressed in a majority of NSCLC tissue microarray (TMA) samples by immunohistochemistry (48). While it has been suggested that ID1 can promote the invasion of NSCLC cells (4), not much informa-tion is known about its role in the growth and progression of NSCLCs. In the present study, we report that ID1 is induced in a wide variety of NSCLC cell lines as well as primary epithelial and endothelial cells from the lung in response to nAChR as well as EGFR signaling.…”

Inhibitor of Differentiation-1 as a Novel Prognostic Factor in NSCLC Patients with Adenocarcinoma Histology and Its Potential Contribution to Therapy Resistance

“…Our analyses showed a significantly higher expression of Id1 protein in tumor tissue compared with normal lung tissue. Recently, Bhattacharya and colleagues (22) compared Id1 mRNA expression levels in NSCLC tumors and matched normal samples in a short series of specimens. Surprisingly, the majority of the 30 tumor samples studied (with AC and SCC histology) showed significantly lower Id1 expression compared with matched normal tissues but no immunohistochemistry analysis was conducted to confirm the presence of the protein.…”

“…21) and NSCLC (20,22). Id1 expression has also been shown in NSCLC (22) at the mRNA level. However, no clear evidence (or even contradictory results) has been published on Id1 expression in tumor tissue compared with normal tissue and the correlation between Id1 levels and patient's clinical outcome has never been addressed.…”

Id-1, Id-2, and Id-3 co-expression correlates with prognosis in stage I and II lung adenocarcinoma patients treated with surgery and adjuvant chemotherapy

“…As we observed that the majority of tumor cells expressed nuclear Ids, we applied a modified H-score, where the extension of nuclear intensity of staining was scored as percentage of positive cells and the intensity of staining was assessed compared with a known external positive control. Actually, there has been uncertainty about staining for Ids and its relationship with different histological type 33,34,37,38 ) and how best to record staining for Ids. Yang et al 42 employed a semi-quantitative score in breast carcinoma classified by plus into four groups: þ, 0-10%; þþ, 10-20%; þþþ, 20-30%; þþþþ, 30-40%.…”