The expression pattern and functional role of REIC/Dkk-3 in the development of cutaneous squamous cell carcinoma

Shin, Jung-Hye; Choi, Dae Eun; Hye-Young, Kang; Sohn, Kyung-Ah; Lee, Young; Kim, Chang Deok; Lee, Jeung‐Hoon; Park, Byung Cheol

doi:10.1016/j.jdermsci.2016.06.006

Cited by 8 publications

(7 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Endogenous Dkk-3 is frequently downregulated in cancers and has been studied as a potential anti-oncogene [17,18]. In our study, we found that Dkk-3 was exceptionally upregulated in bladder cancer T24 cells.…”

Section: Discussionsupporting

confidence: 58%

A Novel Role of Dickkopf-Related Protein 3 in Macropinocytosis in Human Bladder Cancer T24 Cells

Tsujimura

Yamada

Kuranaga

et al. 2016

IJMS

View full text Add to dashboard Cite

Dickkopf-related protein 3 (Dkk-3) is a potential tumor suppressor reported in various cancer entities. However, we found that Dkk-3 was exceptionally upregulated in bladder cancer T24 cells. To validate the biological role of Dkk-3 other than a tumor suppressor, we examined the function of Dkk-3 in T24 cells. Gene silencing of Dkk-3 inhibited cell growth through inducing G0/G1 cell-cycle arrest. Furthermore, Dkk-3 knock-down caused macropinocytosis accompanied by autophagy, which were canceled in part by their inhibitors 5-(N-ethyl-N-isopropyl) amiloride (EIPA) and 3-methyladenine (3-MA). The macropinocytosis was induced by the Dkk-3 knock-down when there were sufficient extracellular nutrients. On the other hand, when the nutritional condition was poor, the autophagy was mainly induced by the Dkk-3 knock-down. These data indicated that Dkk-3 has a role in modulating macropinocytotic and autophagic pathways, a distinct function other than a Wnt antagonist.

show abstract

Section: Discussionsupporting

confidence: 58%

A Novel Role of Dickkopf-Related Protein 3 in Macropinocytosis in Human Bladder Cancer T24 Cells

Tsujimura

Yamada

Kuranaga

et al. 2016

IJMS

View full text Add to dashboard Cite

show abstract

“…Shin et al (22) reported that Dkk3 immunostaining was gradually downregulated from the epidermis in normal skin, actinic keratosis to squamous cell carcinoma (SCC). Dkk3 mRNA expression level was lower in SCC than in normal skin.…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that Dkk3 could cause c-JNK activation, mitochondrial translocation of Bax, and Bcl-2 under-expression in apoptotic induction (4). Shin et al (22) have shown that Ad-Dkk3 induced JNK activation and subsequent apoptosis in lung cancer cells. It has been suggested that expression of cytosolic and secretory Dkk3 protein types might contribute to apoptotic induction of colorectal cancer cells via the mitochondrial pathway.…”

Section: Discussionmentioning

confidence: 99%

The Suppressing Effects of Dkk3 Expression on Aggressiveness and Tumorigenesis of Colorectal Cancer

et al. 2020

View full text Add to dashboard Cite

Dkk3 has been discovered during comparison of immortalized and parental cells. Its expression has been shown to reduce colony formation and induce apoptosis of cancer cells, acting as a tumor suppressor. Herein, we demonstrate that Dkk3 overexpression or protein treatment may inhibit colorectal cancer cell proliferation, migration, and invasion and that they may promote apoptosis and G2 phase arrest with hypoexpression of Bcl-2, cdc25B, cdc25c, N-cadherin, slug, and twist and hyperexpression of Bax and E-cadherin. This effect is consistent with that of recombinant Dkk3 exposure and blocked with anti-Dkk3 antibody. Dkk3 deletion in intestinal cells was not associated with the emergence of epithelial lesions; however, adenoma emerged after sodium desoxycholate treatment. At both mRNA and protein levels, Dkk3 expression was higher in normal than in cancer tissues (p<0.05). Dkk3 mRNA expression was negatively associated with its promoter methylation, growth pattern, differentiation, and favorable prognosis in the patients with colorectal cancer (p<0.05). Dkk3-related signal pathways in colorectal cancer included those of cellular adhesion and migration, melanogenesis, chemokine, Hedgehog, JAK-STAT, TOLL-like receptor, TGF-β, MAPK, and calcium signaling (p<0.05). These findings indicate that Dkk3 expression levels can help assess cancer aggressiveness and patient prognosis. It might also suppress aggressive phenotypes and tumorigenesis as a molecular target in gene therapy.

show abstract

“…A decrease in Dkk3 expression was also detected in cSCCs. Overexpression of Dkk3 in SCC cells significantly reduced proliferation and migration [146], suggesting that Dkk3 has inhibitory effects on SCC development.…”

Section: Wnt Signaling In Keratinocyte Carcinomasmentioning

confidence: 99%

Wnt Signaling Pathways in Keratinocyte Carcinomas

Lang

Chan

Veltri

et al. 2019

Cancers

View full text Add to dashboard Cite

The skin functions as a barrier between the organism and the surrounding environment. Direct exposure to external stimuli and the accumulation of genetic mutations may lead to abnormal cell growth, irreversible tissue damage and potentially favor skin malignancy. Skin homeostasis is coordinated by an intricate signaling network, and its dysregulation has been implicated in the development of skin cancers. Wnt signaling is one such regulatory pathway orchestrating skin development, homeostasis, and stem cell activation. Aberrant regulation of Wnt signaling cascades not only gives rise to tumor initiation, progression and invasion, but also maintains cancer stem cells which contribute to tumor recurrence. In this review, we summarize recent studies highlighting functional evidence of Wnt-related oncology in keratinocyte carcinomas, as well as discussing preclinical and clinical approaches that target oncogenic Wnt signaling to treat cancers. Our review provides valuable insight into the significance of Wnt signaling for future interventions against keratinocyte carcinomas.

show abstract

The expression pattern and functional role of REIC/Dkk-3 in the development of cutaneous squamous cell carcinoma

Cited by 8 publications

References 26 publications

A Novel Role of Dickkopf-Related Protein 3 in Macropinocytosis in Human Bladder Cancer T24 Cells

A Novel Role of Dickkopf-Related Protein 3 in Macropinocytosis in Human Bladder Cancer T24 Cells

The Suppressing Effects of Dkk3 Expression on Aggressiveness and Tumorigenesis of Colorectal Cancer

Wnt Signaling Pathways in Keratinocyte Carcinomas

Contact Info

Product

Resources

About