Epithelial–mesenchymal transition in tumor metastasis

Yeung, Kay T.; Yang, Jing

doi:10.1002/1878-0261.12017

Cited by 561 publications

(486 citation statements)

References 93 publications

Supporting

Mentioning

450

Contrasting

Unclassified

Order By: Relevance

“…Moreover, patients with low expression levels of miR-381 exerted high SOX4 protein expression levels. EMT caused tumor metastasis has been well established (20). Even, in general, SOX4 didn't bind to the promoters of EMT markers to regulate their expression (21), but SOX4 has been demonstrated to promote the EMT in lung cancer (22) and prostate cancer (23).…”

Section: Discussionmentioning

confidence: 99%

“…Even, in general, SOX4 didn't bind to the promoters of EMT markers to regulate their expression (21), but SOX4 has been demonstrated to promote the EMT in lung cancer (22) and prostate cancer (23). Data showed that a SOX4/EZH2 protein complex could be formed to bind to promote serval EMT related transcription factors expression, such as Snail, Zeb, and Twist (20). In order to know whether miR-381/SOX4 axis could regulate the EMT in gastric cancer, we detected three markers of EMT and found that miR-381 overexpression increased the endothelial marker's (E-cadherin) expression whereas inhibited mesenchymal makers' (N-cadherin and vimentin) expression.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

MiR-381 inhibits migration and invasion in human gastric carcinoma through downregulatedting SOX4

Zhang¹,

Huang²,

Long³

2017

Oncology Letters

View full text Add to dashboard Cite

Abstract. Aberrant expression of microRNAs (miRs) serves essential roles in the generation and progression of various types of human cancer. In the present study, the expression and biological functions of miR-381 in human gastric carcinoma (GC) were focused upon. The results of reverse transcription-quantitative polymerase chain reaction analysis revealed that the expression of miR-381 was significantly downregulated in GC tissue samples. Furthermore, low expression of miR-381 was identified to be associated with lymphatic metastasis and advanced tumor-node-metastasis stage (III+IV). Upregulation of miR-381 inhibited the migration and invasion of GC SGC-7901 cells through SRY-Box 4 (SOX4)-mediated epithelial-mesenchymal transition. Finally, long non-coding (lnc) RNA-taurine upregulatedted 1 (non-protein coding) (TUG1) was confirmed as a negatively regulator of miR-381 expression in SGC-7901 cells. Taken together, the results of the current study indicate that the downregulation of miR-381 by lncRNA-TUG1 promoted the metastasis of GC cells by inhibiting SOX4. Thus, targeting miR-381 may be a novel therapeutic option for the treatment of patients with GC.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MiR-381 inhibits migration and invasion in human gastric carcinoma through downregulatedting SOX4

Zhang¹,

Huang²,

Long³

2017

Oncology Letters

View full text Add to dashboard Cite

show abstract

“…SKOV3 (1x10 4 ) and OVCAR3 (5x10 4 ) cells were trypsinized and resuspended in growth medium containing 0.35% agarose (BD Biosciences), and then plated onto a solid layer of 0.7% agarose in growth medium in 6-well plates. Fresh medium (500 µl) was added on alternate days for two weeks.…”

Section: Lentiviral Vector Productionmentioning

confidence: 99%

“…However, the molecular mechanisms underlying the tumor metastasis and chemoresistance in ovarian cancer are not well understood. The epithelial-mesenchymal transition (EMT) contributes to the tumor metastasis and chemoresistance (4). EMT is a biological process accompanied by the loss of cell adherence junctions and apical-basal polarity, and acquisition of the mesenchymal phenotype to increase cell motility and invasiveness (5).…”

Section: Introductionmentioning

confidence: 99%

Lentiviral vector mediated-ASAP1 expression promotes epithelial to mesenchymal transition in ovarian cancer cells

et al. 2018

View full text Add to dashboard Cite

Abstract. Ovarian cancer is one of the most common malignancies in women and has a high mortality rate due to metastatic progression and tumor recurrence. ASAP1 (ArfGAP with SH3 Domain, Ankyrin Repeat and PH Domain 1) is an ADP-ribosylation factor GTPase-activating protein, which is involved in tumor metastasis. However, the role of ASAP1 in ovarian cancer is completely unknown. The present study reported that ASAP1 was highly expressed in ovarian carcinoma, and expression positively-correlated with overall poor survival and prognosis of patients. Lentiviral vector mediated ASAP1 expression promoted cell migration and invasion in ovarian cancer cell lines SKOV3 and OVCAR3. In addition, ASAP1 promoted cell proliferation, survival and inhibited chemotherapy drug paclitaxel-induced cell apoptosis. Furthermore, ASAP1 expression promoted epithelial to mesenchymal transition (EMT) by upregulating the mesenchymal cell markers N-cadherin and vimentin, and downregulating epithelial cell marker E-cadherin in the ovarian cancer cell lines. The data indicate for the first time that ASAP1 exhibits an oncogenic role by promoting EMT in ovarian cancer cells. IntroductionOvarian cancer is one of the most common gynecological malignancies with a high mortality rate (1). In 2017, 22,440 new cases and 14,080 deaths of ovarian cancer were estimated to occur in the United States (2). At the time of diagnosis, the majority of ovarian cancer patients have already progressed to advanced disease, due to the lack of early clinical symptoms, which results in high mortality (3). However, the molecular mechanisms underlying the tumor metastasis and chemoresistance in ovarian cancer are not well understood. The epithelial-mesenchymal transition (EMT) contributes to the tumor metastasis and chemoresistance (4). EMT is a biological process accompanied by the loss of cell adherence junctions and apical-basal polarity, and acquisition of the mesenchymal phenotype to increase cell motility and invasiveness (5). EMT marker gene expression is altered during the EMT process with downregulation of epithelial markers such as E-cadherin and upregulation of mesenchymal markers, including Snai1 and 2, N-cadherin, vimentin, Zeb 1/2, and Twist1/2 (6,7). ASAP1 (ArfGAP with SH3 Domain, Ankyrin Repeat and PH Domain 1) protein has N-terminal BAR, PH, ARF GAP, ankyrin repeat, proline-rich, and C-terminal SH3 domains (8). ASAP1 expression is upregulated in a variety of cancers as compared to normal tissue, and correlates with poor survival and prognosis in colorectal, and neck and head cancer patients (9,10). In breast cancer ASAP1expression contributes to tumor invasion and metastasis (11). ASAP1 is upregulated in ovarian cancer and associated with poor patient survival and prognosis (12). However, the function of ASAP1 in ovarian cancer has not been investigated.In the present study, we investigated the role of ASAP1 in ovarian cancer cells using lentiviral vector mediated overexpression. We demonstrated that ASAP1 was highly expressed in ovarian cancer and as...

show abstract

“…During metastasis, cells invade tissues, migrate through the lymphatic and circulatory systems, travel long distances, and establish in new tissues to form tumors [153]. Although the migration ability of stem cells is repressed after embryonic development, it probably reappears when stem cells or their environments become altered, for example, after tissue injury or under an inflammatory context [162][163][164][165][166]. The activation of developmental programs (e.g., epithelialmesenchymal transition programs) during metastasis can explain why, despite intensive efforts, no genetic mutation has been shown to be required for metastasis [5]; these developmental programs do not require mutations to be activated.…”

Section: The Stem Cell Division Theory Of Cancer Provides a New Framementioning

confidence: 99%

The Stem Cell Division Theory of Cancer

López‐Lázaro

2017

Preprint

View full text Add to dashboard Cite

All cancer registries constantly show striking differences in cancer incidence by age and among tissues. For example, lung cancer is diagnosed hundreds of times more often at age 70 than at age 20, and this cancer in nonsmokers occurs thousands of times more frequently than heart cancer in smokers. An analysis of these differences using basic concepts in cell biology indicates that cancer is the end-result of the accumulation of cell divisions in stem cells. In other words, the main determinant of carcinogenesis is the number of cell divisions that the DNA of a stem cell has accumulated in any type of cell from the zygote. Cell division, process by which a cell copies and separates its cellular components to finally split into two cells, is necessary to produce the large number of cells required for living. However, cell division can lead to a variety of cancer-promoting errors, such as mutations occurring during DNA replication, chromosome aberrations arising during mitosis, errors in the distribution of cell-fate determinants between the daughter cells, and failures to restore physical interactions with other tissue components. Some of these errors are spontaneous, others are promoted by endogenous DNA damage occurring during quiescence, and others are influenced by pathological and environmental factors. The cell divisions required for carcinogenesis are primarily caused by multiple local and systemic physiological signals rather than by errors in the DNA of the cells. As carcinogenesis progresses, the accumulation of DNA errors promotes cell division and eventually triggers cell division under permissive extracellular environments. The accumulation of cell divisions in stem cells drives not only the accumulation of the DNA alterations required for carcinogenesis, but also the formation and growth of the abnormal cell populations that characterize the disease. This model of carcinogenesis provides a new framework for understanding the disease and has important implications for cancer prevention and therapy.

show abstract

Epithelial–mesenchymal transition in tumor metastasis

Cited by 561 publications

References 93 publications

MiR-381 inhibits migration and invasion in human gastric carcinoma through downregulatedting SOX4

MiR-381 inhibits migration and invasion in human gastric carcinoma through downregulatedting SOX4

Lentiviral vector mediated-ASAP1 expression promotes epithelial to mesenchymal transition in ovarian cancer cells

The Stem Cell Division Theory of Cancer

Contact Info

Product

Resources

About