Significance of HIF-1α Expression and LOXL-2 Localization in Progression of Oral Squamous Cell Carcinoma

Bharti, Anshul; Urs, Aadithya B; Kumar, Priya

doi:10.31557/apjcp.2021.22.2.341

Cited by 7 publications

(11 citation statements)

References 25 publications

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“…The increased cell surface concentration of these receptors results in enhanced sensitivity to EGF family ligands, which, in turn, enhances tumor growth and tumor metastasis [ 42 ]. Following these observations, additional evidence has accumulated suggesting that lysyl oxidases, such as LOXL2 and LOX, promote desmoplasia under various conditions and, as a result, promote tumor cells invasiveness and tumor metastasis [ 43 , 44 , 45 , 46 , 47 ]. Furthermore, interference with collagen stabilization by the inhibition of lysyl oxidases significantly enhances responses to chemotherapy in various tumor models, even in metastatic disease [ 48 ].…”

Section: Extracellular Mechanisms By Which Lysyl Oxidases Promote Tum...mentioning

confidence: 99%

Lysyl Oxidase Family Enzymes and Their Role in Tumor Progression

Liburkin-Dan

Toledano

Neufeld

2022

IJMS

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The five genes of the lysyl oxidase family encode enzymes that covalently cross-link components of the extracellular matrix, such as various types of collagen and elastin, and, thus, promote the stabilization of extracellular matrixes. Several of these genes, in particular lysyl oxidase (LOX) and lysyl oxidase like-2 (LOXL2) were identified as genes that are upregulated by hypoxia, and promote tumor cells invasion and metastasis. Here, we focus on the description of the diverse molecular mechanisms by which the various lysyl oxidases affect tumor progression. We also describe attempts that have been made, and are still on-going, that focus on the development of efficient lysyl oxidase inhibitors for the treatment of various forms of cancer, and of diseases associated with abnormal fibrosis.

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Section: Extracellular Mechanisms By Which Lysyl Oxidases Promote Tum...mentioning

confidence: 99%

Lysyl Oxidase Family Enzymes and Their Role in Tumor Progression

Liburkin-Dan

Toledano

Neufeld

2022

IJMS

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“…In contrast, HIF-1α is stabilized in hypoxic tissues, where it cooperates with transcriptional coactivators to induce the expression of target genes [ 206 ]. In this regard, it is noteworthy that high HIF-1α protein levels are detected in advanced, proliferating, and invasive OSCCs [ 207 ].…”

Section: Cd147 and The Growth Of Osccmentioning

confidence: 99%

The Multiple Roles of CD147 in the Development and Progression of Oral Squamous Cell Carcinoma: An Overview

Barillari

Melaiu

Gargari

et al. 2022

IJMS

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Cluster of differentiation (CD)147, also termed extracellular matrix metalloprotease inducer or basigin, is a glycoprotein ubiquitously expressed throughout the human body, the oral cavity included. CD147 actively participates in physiological tissue development or growth and has important roles in reactive processes such as inflammation, immunity, and tissue repair. It is worth noting that deregulated expression and/or activity of CD147 is observed in chronic inflammatory or degenerative diseases, as well as in neoplasms. Among the latter, oral squamous cell carcinoma (OSCC) is characterized by an upregulation of CD147 in both the neoplastic and normal cells constituting the tumor mass. Most interestingly, the expression and/or activity of CD147 gradually increase as healthy oral mucosa becomes inflamed; hyperplastic/dysplastic lesions are then set on, and, eventually, OSCC develops. Based on these findings, here we summarize published studies which evaluate whether CD147 could be employed as a marker to monitor OSCC development and progression. Moreover, we describe CD147-promoted cellular and molecular events which are relevant to oral carcinogenesis, with the aim to provide useful information for assessing whether CD147 may be the target of novel therapeutic approaches directed against OSCC.

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“…However, Bharti et al 26 identified a significantly higher proportion of cases with strong LOXL2 cytoplasmic staining among patients with N0 and N1 disease than among those with N2 disease. No significant differences in LOXL2 staining were identified among the tissues of patients with different tumor stages and AN chewing habits 26 . To the best of our knowledge, no studies have reported the association between LOXL2 expression and survival time in patients with OSCC.…”

Section: Introductionmentioning

confidence: 97%

“…The differences in immunoreactivities were more pronounced in regional lymph node metastasis‐positive OSCCs. However, Bharti et al 26 identified a significantly higher proportion of cases with strong LOXL2 cytoplasmic staining among patients with N0 and N1 disease than among those with N2 disease. No significant differences in LOXL2 staining were identified among the tissues of patients with different tumor stages and AN chewing habits.…”

Section: Introductionmentioning

confidence: 97%

“…No significant differences in LOXL2 staining were identified among the tissues of patients with different tumor stages and AN chewing habits. 26 To the best of our knowledge, no studies have reported the association between LOXL2 expression and survival time in patients with OSCC. In addition, the mechanisms by which LOXL2 affects HNSCC are not well understood.…”

Section: Introductionmentioning

confidence: 98%

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Lysyl oxidase‐like 2 promotes stemness and enhances antitumor effects of gefitinib in head and neck cancer via IFIT1 and IFIT3

Deng

et al. 2023

Cancer Science

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Lysyl oxidase‐like 2 (LOXL2) is a matrix‐remodeling enzyme that has recently been identified as an important regulator of tumor progression and metastasis. This study discovered that LOXL2 expression in oral squamous cell carcinoma (OSCC) tissues was significantly associated with tumor clinical stage, lymph node metastasis and patients' overall survival time. LOXL2‐overexpressing human buccal SCC TW2.6 (TW2.6/LOXL2) and hypopharyngeal SCC FaDu (FaDu/LOXL2) cells exhibited enhanced migration, invasion, epithelial–mesenchymal transition (EMT), and cancer stem cell (CSC) phenotypes, independently of its enzymatic activity. Moreover, TW2.6/LOXL2 significantly increased tumor‐initiating frequency in SCID mice. We further demonstrated that LOXL2 increased the levels of interferon‐induced protein with tetratricopeptide repeats 1 (IFIT1) and IFIT3 in TW2.6/LOXL2 and FaDu/LOXL2 cells. We also identified IFIT1 and IFIT3 as key downstream components of LOXL2 action in migration, invasion, EMT, and CSC phenotypes in TW2.6 and FaDu cells. Furthermore, a significant positive correlation between LOXL2 expression and IFIT1 and IFIT3 overexpression in human OSCC tissues was observed. In addition, TW2.6/LOXL2 and FaDu/LOXL2 cells were 3.3‐ to 3.6‐fold more susceptible to the epidermal growth factor receptor (EGFR) inhibitor gefitinib than were their respective control cells. The antitumor effect of gefitinib on orthotopic TW2.6/LOXL2 xenograft tumor was fourfold higher than that on controls. Our results indicate that LOXL2 expression is a strong prognostic factor for OSCC and may be used as a marker to identify patients most likely to respond to EGFR‐targeted therapy.

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Significance of HIF-1α Expression and LOXL-2 Localization in Progression of Oral Squamous Cell Carcinoma

Cited by 7 publications

References 25 publications

Lysyl Oxidase Family Enzymes and Their Role in Tumor Progression

Lysyl Oxidase Family Enzymes and Their Role in Tumor Progression

The Multiple Roles of CD147 in the Development and Progression of Oral Squamous Cell Carcinoma: An Overview

Lysyl oxidase‐like 2 promotes stemness and enhances antitumor effects of gefitinib in head and neck cancer via IFIT1 and IFIT3

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