Overexpression Cathepsin D Contributes to Perineural Invasion of Salivary Adenoid Cystic Carcinoma

Zhang, Mei; Wu, Jian; Yang, Xiao; Pang, Xin; Li, Li; Wang, Shasha; Wu, Jing‐biao; Tang, Ya‐Jie; Liang, Xin‐hua; Zheng, Min; Tang, Yaling

doi:10.3389/fonc.2018.00492

Cited by 18 publications

(19 citation statements)

References 42 publications

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“…PNI, a hallmark of SACC, is an independent indicator of tumor recurrence and a poor prognosis ( 44 - 46 ). The role of cathepsins in PNI of SACC was also demonstrated in our previous study, in which cathepsin D was overexpressed in the nerve invasion frontier and associated with a poor prognosis of patients with SACC ( 47 ).…”

Section: Discussionsupporting

confidence: 75%

Cathepsin B defines leader cells during the collective invasion of salivary adenoid cystic carcinoma

Wang

et al. 2019

Int J Oncol

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Cathepsin B (CTSB) has been reported to be involved in cancer metastasis by altering extracellular matrix (ECM) remodeling and facilitating invasion. However, the contribution of CTSB to collective cell invasion in salivary adenoid cystic carcinoma (SACC) and the underlying mechanisms remain unclear. The present study demonstrated that collective cell invasion is commonly observed in SACC without a complete epithelial-mesenchymal transition signature. CTSB was found to be overexpressed in the invasive front of SACC compared to the tumor center, and was associated with a poor prognosis of patients with SACC. Subsequently, a 3D spheroid invasion assay was established in order to recapitulate the collective cell invasion of SACC and the results revealed that CTSB was only expressed in leader cells. The knockdown of CTSB by siRNA inhibited the migration and invasion of SACC-83 cells and impaired the formation of leader cells. CTSB knockdown also disrupted cytoskeletal organization, altered cell morphology and inhibited ECM remodeling by downregulating matrix metalloproteinase-9, focal adhesion kinase and Rho/ROCK function. Therefore, the present study provides evidence that CTSB may define leader cells in SACC and is required for collective cell invasion as a potential key regulator of ECM remodeling.

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Section: Discussionsupporting

confidence: 75%

Cathepsin B defines leader cells during the collective invasion of salivary adenoid cystic carcinoma

Wang

et al. 2019

Int J Oncol

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“…In this study, we have used a proteomic approach to identify proteins in the secretome of L1-overexpressing CRC cells whose levels are increased after L1 expression and that might be involved in the L1-mediated promotion of tumor development. We identified the lysosomal and secreted aspartate protease CTSD and focused on studying its role in CRC development, since it was reported that CTSD is expressed in a wide variety of tumor types including breast cancer [22–28], prostate cancer [29], gastric cancer [30], osteosarcoma pulmonary metastases, bone cancer [31], ovarian cancer [32] and in liver metastases of colon adenocarcinoma [33–35]. We found that in addition to the increased abundance of CTSD in the secretome of L1-overexpressing CRC cells, CTSD RNA and protein levels were also higher in CRC cell lines overexpressing L1.…”

Section: Discussionmentioning

confidence: 99%

Increased expression of cathepsin D is required for L1-mediated colon cancer progression

et al. 2019

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Hyperactivation of Wnt/β-catenin target genes is considered a key step in human colorectal cancer (CRC) development. We previously identified the immunoglobulin-like cell adhesion receptor L1 as a target gene of β-catenin/TCF transactivation that is localized at the invasive edge of CRC tissue. Using gene arrays, we discovered a number of downstream target genes and signaling pathways conferred by L1 overexpression during colon cancer progression. Here, we have used a proteomic approach to identify proteins in the secretome of L1-overexpressing CRC cells and studied the role of the increase in the aspartate protease cathepsin D (CTSD) in L1-mediated colon cancer development. We found that in addition to the increase in CTSD in the secretome, the RNA and protein levels of CTSD were also induced by L1 in CRC cells. CTSD overexpression resulted in elevated proliferation under stress and increased motility, tumorigenesis and liver metastasis, although to a lesser extent than after L1-transfection. The suppression of endogenous CTSD in L1-expressing cells blocked the increase in the proliferative, motile, tumorigenic and metastatic ability of CRC cells. Enhancing Wnt/β-catenin signaling by the inhibition of GSK3β resulted in increased endogenous CTSD levels, suggesting the involvement of the Wnt/β-catenin pathway in CTSD expression. In human CRC tissue, CTSD was detected in epithelial cells and in the stromal compartment at the more invasive areas of the tumor, but not in the normal mucosa, indicating that CTSD plays an essential role in CRC progression.

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“…MMP-7, kalikrein 10, cathepsin V, MMP-2, and cathepsin D are reported to be involved in cancer invasion, especially MMP-2 as an invadopodia-recruited protease that is involved in the matrix-degrading capability. 14,20-24…”

Section: Discussionmentioning

confidence: 99%

Anti-invasive and Anti-tumor Effects of Dryopteris crassirhizoma Extract by Disturbing Actin Polymerization

et al. 2019

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Aim . To evaluate the anti-invasive effect of ethanol extracts of rhizome of Dryopteris crassirhizoma (EEDC) in matrix invasion and formation of functional invadopodia and to determine the anti-tumor effect of EEDC in a mouse model of mandibular invasion by gingival squamous cell carcinoma (SCC). Methods . The rhizome of D crassirhizoma was extracted in ethanol. The anti-invasive effect of EEDC was analyzed with a Matrigel-coated transwell invasion and 3D culture system. Crucial factors related to the control of cancer cell invasion by EEDC were determined using a human protease array. Molecular evidence supporting the anti-invasive effect of EEDC in oral SCC (OSCC) cells used an invadopodia-mediated extracellular matrix (ECM) degradation; an in vivo athymic mouse model was also provided. Results . EEDC treatment (10 µg/mL) suppressed transwell migration and invasion of HSC-3 OSCC cells without cytotoxicity. Decreased levels of matrix metalloprotease (MMP)-7, kalikrein 10, cathepsin V, MMP-2, and cathepsin D were also found in EEDC-treated HSC-3 cells based on human protease array. The anti-invasive effects of EEDC involved the suppression of invadopodia-mediated ECM degradation via inhibition of globular-actin elongation. The anti-invasive effect resulting from disturbance of functional invadopodia formation by EEDC was observed even at a low concentration of 5 µg/mL. The phosphorylation of cortactin involved in functional invadopodia formation was decreased at EEDC concentrations that inhibited invadopodia formation. The anti-tumor effect of EEDC was also observed in a mouse xenograft model. Administration of EEDC resulted in inhibition of tumor growth and progression. Conclusions . EEDC represents a potential anti-invasive and anti-tumor agent in cancer control.

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Overexpression Cathepsin D Contributes to Perineural Invasion of Salivary Adenoid Cystic Carcinoma

Cited by 18 publications

References 42 publications

Cathepsin B defines leader cells during the collective invasion of salivary adenoid cystic carcinoma

Cathepsin B defines leader cells during the collective invasion of salivary adenoid cystic carcinoma

Increased expression of cathepsin D is required for L1-mediated colon cancer progression

Anti-invasive and Anti-tumor Effects of Dryopteris crassirhizoma Extract by Disturbing Actin Polymerization

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