Aberrant expression of the tight junction molecules claudin-1 and zonula occludens-1 mediates cell growth and invasion in oral squamous cell carcinoma

Babkair, Hamzah; Yamazaki, Manabu; Uddin, Md. Shihab; Maruyama, Satoshi; Abé, Tatsuya; Essa, Ahmed; Sumita, Yoshimasa; Ahsan, Md. Shahidul; Swelam, Wael; Cheng, Jun; Saku, Takashi

doi:10.1016/j.humpath.2016.07.001

Cited by 23 publications

(23 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The elevation of tumor invasion is supported by our sequencing results that demonstrated TNFα up-regulates invasion-related genes of MMP1, MMP9, MMP14, LAMB3, and FGF2 which all have been previously reported to increase OSCC cancer invasion [ 27 – 29 ]. Likewise, we also showed that TNFα up-regulate genes CLDN-1, IL6, and NFκBIA, which have previously been reported to increase OSCC cell proliferation, supporting our increased tumor volume findings [ 30 – 32 ].…”

Section: Discussionsupporting

confidence: 91%

Oral inflammation promotes oral squamous cell carcinoma invasion

et al. 2018

View full text Add to dashboard Cite

Oral squamous cell carcinoma (OSCC) represents 95% of oral malignancies and invasion, and metastasis underlies disease morbidity and mortality. We recently established a direct link between oral inflammation and cancer invasion by showing that neutrophils increase OSCC invasion through a tumor necrosis factor (TNFα)-dependent mechanism. The objective of this study was to characterize OSCC-associated inflammation and to determine the molecular mechanisms underlying inflammation-mediated OSCC invasion. Our results showed a significant increase in neutrophil infiltration, the neutrophil-to-lymphocyte ratio in the OSCC microenvironment and increased inflammatory markers, particularly TNFα in saliva. We performed next-generation sequencing of the TNFα-treated OSCC cells and showed marked overexpression of over 180 genes distributed among clusters related to neutrophil recruitment, invasion, and invadopodia. At the molecular level, TNFα treatment increased phosphoinositide 3-kinase (PI3K)-mediated invadopodia formation and matrix metalloproteinase (MMP)-dependent invasion. We show here that TNFα promotes a pro-inflammatory and pro-invasion phenotype leading to the recruitment and activation of inflammatory cells in a paracrine mechanism. Increased TNFα in the tumor microenvironment tips the balance towards invasion leading to decreased overall survival and disease-free survival. This represents a significant advancement of oral cancer research and will support new treatment approaches to control OSCC invasion and metastasis.

show abstract

Section: Discussionsupporting

confidence: 91%

Oral inflammation promotes oral squamous cell carcinoma invasion

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Cell surface expression of E-cadherin was decreased on LP-1/Cfz cells compared to parental LP-1 cells [ 8 ], but TJP1 protein levels were predicted to be ~2-fold increased ( Table S1 : Expression changes, TJP1 202011_at probe set). Of potential relevance in this regard, upregulation of TJP1 has been associated with invasion and metastasis in certain tumor systems [ 28 - 30 ].…”

Section: Resultsmentioning

confidence: 99%

Increased expression of the tight junction protein TJP1/ZO-1 is associated with upregulation of TAZ-TEAD activity and an adult tissue stem cell signature in carfilzomib-resistant multiple myeloma cells and high-risk multiple myeloma patients

Riz

Hawley

2017

Oncoscience

View full text Add to dashboard Cite

Tight junction protein 1 (TJP1) has recently been proposed as a biomarker to identify multiple myeloma (MM) patients most likely to respond to bortezomib- and carfilzomib-based proteasome inhibitor regimens. Herein we report increased expression of TJP1 during the adaptive response mediating carfilzomib resistance in the LP-1/Cfz MM cell line. Moreover, increased TJP1 expression delineated a subset of relapsed/refractory MM patients on bortezomib-based therapy sharing an LP-1/Cfz-like phenotype characterized by activation of interacting transcriptional effectors of the Hippo signaling cascade (TAZ and TEAD1) and an adult tissue stem cell signature. siRNA-mediated knockdown of TJP1 or TAZ/TEAD1 partially sensitized LP-1/Cfz cells to carfilzomib. Connectivity Map analysis identified translation inhibitors as candidate therapeutic agents targeting this molecular phenotype. We confirmed this prediction by showing that homoharringtonine (omacetaxine mepesuccinate) — the first translation inhibitor to be approved by the U.S. Food and Drug Administration — displayed potent cytotoxic activity on LP-1/Cfz cells. Homoharringtonine treatment reduced the levels of TAZ and TEAD1 as well as the MM-protective proteins Nrf2 and MCL1. Thus, our data suggest the importance of further studies evaluating translation inhibitors in relapsed/refractory MM. On the other hand, use of TJP1 as a MM biomarker for proteasome inhibitor sensitivity requires careful consideration.

show abstract

“…39 A microarray data indicated low to an absence of CLDN-1 expression in moderate and poorly differentiated OSCC, 40 which contradicts not only ours but many other findings. 20,21 Significantly higher CLDN-1 expression in patients with hypopharyngeal squamous cell carcinoma was found to be associated with the degree of tumor differentiation. 41 A study performed to check the role of CLDN-1 in OSCC cell lines indicated a relationship between OSCC and extracellular matrix components.…”

Section: Discussionmentioning

confidence: 98%

Joint detection of claudin‐1 and junctional adhesion molecule‐A as a therapeutic target in oral epithelial dysplasia and oral squamous cell carcinoma

Upadhaya

Barhoi

Giri

et al. 2019

J of Cellular Biochemistry

View full text Add to dashboard Cite

Abnormal expression of claudin‐1 (CLDN‐1) and junctional adhesion molecule‐A (JAM‐A) has been described in certain malignancies but their clinical relevance is poorly understood. The present study aims to elucidate the role of CLDN‐1 and JAM‐A in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Changes in the expression of these proteins were identified immunohistochemically on tissue sections from patients with OED and OSCC and compared with control. A correlation between the expression level of proteins and clinicopathological features was analyzed by Pearson's correlation χ2 test. The survival curve of the follow‐up data was estimated by the Kaplan‐Meier method followed by the log‐rank test. CLDN‐1 and JAM‐A were highly expressed in OED and OSCC tissues when compared to control. Also, delocalization of CLDN‐1 from the membrane to the cytoplasm to the nucleus was observed as the cell proceeds from normal to malignancy. Increased expression of CLDN‐1 and JAM‐A in both OED and OSCC were concomitant with histological grades. In addition, increased JAM‐A was associated with perineural invasion of cancer cells. A positive correlation between the expression level of proteins was observed in OED (r = 0.733) and OSCC (r = 0.577). Kaplan‐Meier analysis in patients with OSCC showed that the survival rate was lower in patients with high CLDN‐1 and high JAM‐A expression compared to low expressed patients. To conclude, the elevated level and delocalization of CLDN‐1 and JAM‐A suggest their use as tumor markers. A positive correlation between CLDN‐1 and JAM‐A suggests joint detection of these proteins as a future diagnostic tool in oral precancerous and cancerous conditions.

show abstract

Aberrant expression of the tight junction molecules claudin-1 and zonula occludens-1 mediates cell growth and invasion in oral squamous cell carcinoma

Cited by 23 publications

References 37 publications

Oral inflammation promotes oral squamous cell carcinoma invasion

Oral inflammation promotes oral squamous cell carcinoma invasion

Increased expression of the tight junction protein TJP1/ZO-1 is associated with upregulation of TAZ-TEAD activity and an adult tissue stem cell signature in carfilzomib-resistant multiple myeloma cells and high-risk multiple myeloma patients

Joint detection of claudin‐1 and junctional adhesion molecule‐A as a therapeutic target in oral epithelial dysplasia and oral squamous cell carcinoma

Contact Info

Product

Resources

About