Restoration of S100A4 expression enhances invasive and metastatic potentials of COLO16 cutaneous squamous cancer cells

Liu, Yu; Li, Yan; Liu, Cong; Li, Hong; Wu, Mo‐Li; Liu, Zhili; Kong, Qing‐You; Chen, Xiaoyan; Liu, Xiaoyu; Liu, An; Liu, Jia

doi:10.3233/cbm-140414

Cited by 4 publications

(4 citation statements)

References 27 publications

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“…Next, our study demonstrated that silencing of S100A4 restrained the viability, migration, and invasion of rCSCs in virto. 8 , 37 , 38 The promotion in cancer cell migration and invasion mediated by overexpression of S100A4 has been suggested in several human cancers, such as cutaneous squamous cancer, 39 hepatocellular carcinoma, 40 and squamous cell laryngeal cancer. 41 Our study suggested that S100A4 also modulated those capacities of rCSCs, through which S100A4 silencing was conducive to wound repair.…”

Section: Discussionmentioning

confidence: 99%

S100A4 Silencing Facilitates Corneal Wound Healing After Alkali Burns by Promoting Autophagy via Blocking the PI3K/Akt/mTOR Signaling Pathway

Wang

Gao

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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Purpose This study investigated the role of S100 calcium binding protein A4 (S100A4) in corneal wound healing and the underlying mechanism of the S100A4-mediated PI3K/Akt/mammalian target of rapamycin (mTOR) pathway. Methods The rabbit corneal alkali burn model was established in vivo. S100A4 expression, wound healing, inflammation, and autophagy in rabbit cornea after alkali burn were detected. The NaOH-treated rabbit corneal stromal cells (rCSCs) were transfected with overexpressed S100A4 or silencing S100A4 to examine the effect of S100A4 on corneal wound healing in vitro. The effect of S100A4 on cell viability, proliferation, migration, invasion, fibrosis, and autophagy of rCSCs after alkali burn was analyzed. Then the functional rescue experiments were carried out. The PI3K inhibitor, LY294002, was used to elucidate the PI3K/Akt/mTOR signaling pathway in rCSCs. Results S100A4 silencing promoted rabbit corneal wound healing by inhibiting fibrosis and inflammation and promoting autophagy in alkali-burned cornea, corresponding to increased levels of LC3, Beclin 1, and Atg4B but lowered α-smooth muscle actin, TNF-ɑ, and p62 levels. Moreover, silencing S100A4 inhibited proliferation, migration, invasion, and fibrosis of NaOH-treated rCSCs and promoted the differentiation of rCSCs into corneal cells and the autophagy of damaged rCSCs. The inhibitory role of S100A4 in wound healing was achieved via activation of the PI3K/Akt/mTOR pathway. Conclusions S100A4 silencing confers a promising effect on wound healing of alkali-burned cornea by blocking the PI3K/Akt/mTOR pathway, supporting the advancement of corneal gene therapies for wound healing.

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Section: Discussionmentioning

confidence: 99%

S100A4 Silencing Facilitates Corneal Wound Healing After Alkali Burns by Promoting Autophagy via Blocking the PI3K/Akt/mTOR Signaling Pathway

Wang

Gao

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…S100A4 is regarded as an important regulator of metastasis and EMT . Overexpression of S100A4 promotes metastasis in several experimental animal models, in contrast, down‐regulation of S100A4 expression reduces the metastatic capacity of cancer cells . In CRC, S100A4 is overexpressed and its expression is correlated with patient outcome .…”

Section: Discussionmentioning

confidence: 99%

“…[51][52][53] Overexpression of S100A4 promotes metastasis in several experimental animal models, in contrast, down-regulation of S100A4 expression reduces the metastatic capacity of cancer cells. 24,51,[54][55][56][57][58] In CRC, S100A4 is overexpressed and its expression is correlated with patient outcome. 59,60 Consistent with that, our results showed that the expression of S100A4 was higher in human CRC tissues compared with their normal counterpart tissues, and higher expression of S100A4 was significantly correlated with lymph node metastasis and poor survival.…”

Section: Trx-1 Knockdown Inhibits Crc Cell Migration and Invasion Abimentioning

confidence: 99%

Interplay between Trx‐1 and S100P promotes colorectal cancer cell epithelial–mesenchymal transition by up‐regulating S100A4 through AKT activation

Zuo

Zhang

Lin

et al. 2018

J Cellular Molecular Medi

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We previously reported a novel positive feedback loop between thioredoxin‐1 (Trx‐1) and S100P, which promotes the invasion and metastasis of colorectal cancer (CRC). However, the underlying molecular mechanisms remain poorly understood. In this study, we examined the roles of Trx‐1 and S100P in CRC epithelial‐to‐mesenchymal transition (EMT) and their underlying mechanisms. We observed that knockdown of Trx‐1 or S100P in SW620 cells inhibited EMT, whereas overexpression of Trx‐1 or S100P in SW480 cells promoted EMT. Importantly, S100A4 and the phosphorylation of AKT were identified as potential downstream targets of Trx‐1 and S100P in CRC cells. Silencing S100A4 or inhibition of AKT phosphorylation eliminated S100P‐ or Trx‐1‐mediated CRC cell EMT, migration and invasion. Moreover, inhibition of AKT activity reversed S100P‐ or Trx‐1‐induced S100A4 expression. The expression of S100A4 was higher in human CRC tissues compared with their normal counterpart tissues and was significantly correlated with lymph node metastasis and poor survival. The overexpression of S100A4 protein was also positively correlated with S100P or Trx‐1 protein overexpression in our cohort of CRC tissues. In addition, overexpression of S100P reversed the Trx‐1 knockdown‐induced inhibition of S100A4 expression, EMT and migration and invasion in SW620 cells. The data suggest that interplay between Trx‐1 and S100P promoted CRC EMT as well as migration and invasion by up‐regulating S100A4 through AKT activation, thus providing further potential therapeutic targets for suppressing the EMT in metastatic CRC.

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“…S100A4 is also named as FSP (fibroblast‐specific protein) because of its preferable expression in fibroblasts (Österreicher et al, ) or Mts1 (metastasin) as its close correlation with cancer metastasis (Rasanen et al, ). Consequently, S100A4 silencing inhibits invasive ability of human colorectal and pancreatic cancer cells (Dahlmann et al, ; Li et al, ), and restoration of its expression enhances metastatic potential of squamous cell carcinoma of the skin (Yu et al, ).…”

Section: Introductionmentioning

confidence: 99%

Inversed Expression Patterns of S100A4 and E‐Cadherin in Cervical Cancers: Implication in Epithelial–Mesenchymal Transition

Liu

Yang

et al. 2017

The Anatomical Record

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Cervical cancer/CC is the third commonest female malignancy worldwide. The aggressive growth and distal metastases are the leading causes of CC mortality, which is largely due to epithelial-mesenchymal transition/EMT. Fibroblast specific protein S100A4 promotes cancer metastasis and epithelial type cadherin/E-cadherin play pivotal roles in cell-cell and cell-extracellular matrix interaction. Therefore, the expression patterns of S100A4 and E-cadherin reflect statuses of EMT of carcinoma cells. However, S100A4 expression and its relevance with E-cadherin and HPV16 infection in cervical cancers remain unknown. This study aims to address the above issues using cervical cancer specimens. Immunohistochemistry reveals that the levels of mesenchymal marker S100A4 is upregulated (>++) in cervical adenocarcinomas/CACs (12/16; 75%) and squamous cell carcinomas/CSCCs (23/28; 82%) than that in noncancerous glandular epithelia/GE (0/12; 0%) and squamous epithelia/SE (0/12; 0%). Epithelial marker membranous E-cadherin is remarkably reduced on the surface of CAC and CSCC cells (P = 0.00; P = 0.00), especially those showing poorly differentiated phenotypes (P < 0.05) in comparison with their noncancerous counterparts. Correlative analyses revealed an inverse relationship between S100A4 and E-cadherin expression among the cervical cancer samples (P = 0.01, r = -0.38). S100A4 expression level in HPV16-infected group is higher than that in HPV16-free group (P = 0.02). These results suggest the close correlation of S100A4 upregulation with cervical cancer formation and HPV16 infection and E-cadherin reduction with the grades of CC dedifferentiation. The concurrent gain of S100A4 and loss of membrane E-cadherin suggest EMT tendency of CC cells and can be regarded as an unfavorable prognostic parameter of CC patients. Anat Rec, 300:2184-2191, 2017. © 2017 Wiley Periodicals, Inc.

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Restoration of S100A4 expression enhances invasive and metastatic potentials of COLO16 cutaneous squamous cancer cells

Cited by 4 publications

References 27 publications

S100A4 Silencing Facilitates Corneal Wound Healing After Alkali Burns by Promoting Autophagy via Blocking the PI3K/Akt/mTOR Signaling Pathway

S100A4 Silencing Facilitates Corneal Wound Healing After Alkali Burns by Promoting Autophagy via Blocking the PI3K/Akt/mTOR Signaling Pathway

Interplay between Trx‐1 and S100P promotes colorectal cancer cell epithelial–mesenchymal transition by up‐regulating S100A4 through AKT activation

Inversed Expression Patterns of S100A4 and E‐Cadherin in Cervical Cancers: Implication in Epithelial–Mesenchymal Transition

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