The role of the tumor-microenvironment in lung cancer-metastasis and its relationship to potential therapeutic targets

Wood, Steven L.; Pernemalm, Maria; Crosbie, Philip; Whetton, Anthony D.

doi:10.1016/j.ctrv.2013.10.001

Cited by 382 publications

(304 citation statements)

References 119 publications

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“…The extracellular matrix (ECM) plays a significant role in cell growth and migration, as a number of growth-signaling inputs, including Wnt, Notch, and hormone and integrin signaling, emanate from the cytokines and growth factors secreted into the ECM (43,44). The matrix metalloproteinases (MMPs) are also integral components of the signaling process in normal cell migration and tumor cell invasion and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Cystatin E/M Suppresses Tumor Cell Growth through Cytoplasmic Retention of NF-κB

Soh

Venkatesan

Veena

et al. 2016

Molecular and Cellular Biology

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Cervical cancer is the second-most-common cancer responsible for cancer-related death in women around the world. The incidence is increasing, with 450,000 new cases diagnosed worldwide and 12,340 diagnosed in the United States annually (1, 2). It is the third leading cause of death from cancer in women 15 to 34 years of age and the fifth leading cause of death in women 35 to 54 years of age, representing about 2% of all cancers in women in the United States. The disease is frequently found in women who have had multiple sex partners, smoking habits, and immune system dysfunctions (3). Cervical cancer is closely linked with human papillomavirus (HPV) infection, and HPVs are detected in 90% of cervical cancer lesions (4-6). While the E6 protein of HPV inactivates p53 and E7 inactivates the retinoblastoma (Rb) tumor suppressor protein, detailed studies on a large number of tumors indicate that viral infection alone is not sufficient for tumor development. Studies have also shown that 20 to 30 million Americans are infected with HPV (7). However, only those in a subset develop cervical cancer. Recently, HPVs have been implicated in the development of head and neck, lung, and breast cancers (8-10).Cystatins are inhibitors of cysteine proteases and are classified into a large superfamily subdivided into three families based on their location, size, and complexity of polypeptide chains (11-13). Cystatin E/M belongs to the type 2 cystatin family (cystatin C, D, E/M, F, S, SA, and SN), whose members are mainly secreted, and most of them are found abundantly in body fluids and tissues. Cystatin E/M is present as an unglycosylated 14-kDa form containing 149 amino acids and a 17-kDa form that is glycosylated. Loss of this protein seems to play a significant role in abnormal skin development (14). A null mutation of the mouse cystatin E/M gene is also correlated with development of the ichq phenotype, characterized by neonatal lethality, abnormal cornification, and desquamation. Cystatin E/M was initially identified as a downregulated transcript in metastatic breast cancers (15,16). A number of studies have implicated cystatin E/M as a human tumor suppressor gene that is inactivated in the cancers of the breast, cervix, prostate, brain, and stomach (17-23). Our studies have also shown that the inactivation of the gene is associated with homozygous deletion, promoter hypermethylation, and somatic mutations in primary tumor samples (19). Cystatin E/M gene is expressed in ductal carcinoma in situ (DCIS) but not in metastatic breast cancer, pointing to inactivation during tumor progression (16)(17)(18)24). Finally, inactivation of cystatin E/M gene is associated with the loss of expression of estrogen and progesterone receptors and HER4, indicating an association with these proteins in the development of invasive breast cancers (25). However, the molecular mechanism of cystatin E/M-mediated tumor cell growth inhibition is not yet understood.Cathepsins include a broad range of proteases, the serine (A

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Section: Discussionmentioning

confidence: 99%

Cystatin E/M Suppresses Tumor Cell Growth through Cytoplasmic Retention of NF-κB

Soh

Venkatesan

Veena

et al. 2016

Molecular and Cellular Biology

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“…The mechanisms of action could be enzymatic inhibition, metabolic disorder and other intracellular approaches or inter-cellular communication disturbance of the tumoral cells. Moreover, acting on the tumormicroenvironment [27] and create an unbalances within the homeostatic status through targeting the irrigation and the blood supply to the tumoral cells by cryotherapy or surgery represent another approach.…”

Section: Editorialmentioning

confidence: 99%

How can we Imagine the Future of Anti-Tumors Therapies?

Ghanemi¹

2014

JNSK

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“…Irrespective of the progress made in diagnosis and therapy, the prognosis of patients with lung adenocarcinoma remains poor (2). A primary feature of lung adenocarcinoma is the migration and invasion of neoplasms, which are responsible for the high mortality rate (3). Therefore, understanding the mechanisms underlying metastasis in lung adenocarcinoma may reveal novel therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of the long noncoding RNA CCAT1 promotes metastasis via epithelial‑to‑mesenchymal transition in lung adenocarcinoma

et al. 2018

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Abstract. The long noncoding RNA (lncRNA) colon cancer-associated transcript 1 (CCAT1) has been identified as an oncogene in multiple types of human malignancy, and the aberrant expression of CCAT1 has been associated with the tumorigenesis and progression of cancer. However, the underlying mechanism of how CCAT1 affects malignant behaviors in lung adenocarcinoma cells remains unknown. In the current study, the expression of CCAT1 was identified to be increased in lung adenocarcinoma tissues (n=96) by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and its expression level was associated with epidermal growth factor receptor (EGFR) expression (P=0.011), lymphatic metastasis (P=0.003) and tumor node metastasis (TNM) stage (P=0.003). In vitro, by using Transwell assays, the overexpression of CCAT1 was demonstrated to promote the migration and invasion of H358 lung adenocarcinoma cells; while downregulation of CCAT1 expression inhibited H1650 cell migration and invasion. Furthermore, western blot analysis indicated that aberrant CCAT1 expression may induce epithelial-to-mesenchymal transition (EMT) by regulating the expression levels of EMT markers (E-cadherin, N-cadherin and vimentin). In conclusion, these results indicate that CCAT1 is able to promote the metastasis of lung adenocarcinoma cells by inducing EMT.

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The role of the tumor-microenvironment in lung cancer-metastasis and its relationship to potential therapeutic targets

Cited by 382 publications

References 119 publications

Cystatin E/M Suppresses Tumor Cell Growth through Cytoplasmic Retention of NF-κB

Cystatin E/M Suppresses Tumor Cell Growth through Cytoplasmic Retention of NF-κB

How can we Imagine the Future of Anti-Tumors Therapies?

Overexpression of the long noncoding RNA CCAT1 promotes metastasis via epithelial‑to‑mesenchymal transition in lung adenocarcinoma

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