Isoliquiritigenin Reverses Epithelial-Mesenchymal Transition Through Modulation of the TGF-β/Smad Signaling Pathway in Endometrial Cancer

Chen, Hsin Yuan; Chiang, Yi Fen; Huang, Jing; Huang, Tsui-Chin; Shih, Yin Hwa; Wang, Kai-Lee; Ali, Mohamed; Hong, Yong Han; Shieh, Tzong‐Ming; Hsia, Shih Min

doi:10.3390/cancers13061236

Cited by 26 publications

(26 citation statements)

References 47 publications

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“…EMT is one of the classical modes of tumourigenic invasion and metastases. 17 , 27 Many studies 29 , 30 have shown that Smad2/3 plays a central role in TGF-β-induced EMT. At the amino acid level, the most important difference between Smad2 and Smad3 is that the MH1 region of Smad2 has 2 more amino acid fragments than Smad3.…”

Section: Discussionmentioning

confidence: 99%

M2-Type Macrophages Induce Tregs Generation by Activating the TGF-β/Smad Signalling Pathway to Promote Colorectal Cancer Development

Ma¹,

Gao²,

Chen³

et al. 2021

OTT

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Purpose:The increase of both M2-type macrophages and Tregs is closely associated with the development of colorectal cancer. However, the mechanism of their interaction is still unclear. In this study, we investigated the correlation of M2-type macrophages with Tregs and the possible mechanisms between them. Methods: Using immunohistochemistry, we analysed Smad3 (a key protein in the TGF-β/ Smad signalling pathway) expression in colorectal cells, as well as infiltrating numbers of CD163 (a marker for M2-type macrophages), Foxp3 (a marker for Tregs) in 250 surgically resected colorectal cancer tissues, matched normal and paracancerous tissues. The relation of CD163 and Foxp3 was investigated in CRC with clinicopathological characteristics and preoperative tumour markers. Results: CD163, Foxp3 and Smad3 were upregulated in CRC tissues compared to matched normal and paracancerous tissues. Interestingly, CD163 and Foxp3 were significantly positively correlated in CRC, and both were significantly positively correlated with Smad3. Both CD163 and Foxp3 were upregulated with increasing tumour TNM staging, increasing number of lymph node metastases and increasing vascular invasion. Additionally, CD163 was upregulated with increasing depth of infiltration. The number of M2-type macrophages and the expression levels of preoperative CEA, CA19-9 and CA72-4 were significantly positively correlated. The number of Tregs was significantly positively correlated with the expression levels of preoperative CEA and CA19-9. Conclusion: M2-type macrophages may induce Tregs generation through activation of the TGF-β/Smad signalling pathway, which can promote the development of colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

M2-Type Macrophages Induce Tregs Generation by Activating the TGF-β/Smad Signalling Pathway to Promote Colorectal Cancer Development

Ma¹,

Gao²,

Chen³

et al. 2021

OTT

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“…At the same time, the expression of key transcription factors also acts as the driving force for EMT, such as TWIST1, TWIST2, ZEB1, ZEB2, SNAI1 and SNAI2 [ 16 , 17 ]. The critical role of EMT in the metastasis of various tumors has been clearly demonstrated by previous studies, including ovarian tumor [ 18 ], Endometrial Cancer [ 19 ] and nasopharyngeal carcinoma [ 20 ]. However, the upstream regulators for the EMT in CRC remain to be identified.…”

Section: Introductionmentioning

confidence: 99%

B7 family member H4 induces epithelial-mesenchymal transition and promotes the proliferation, migration and invasion of colorectal cancer cells

et al. 2021

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Colorectal cancer (CRC) is a common malignancy of the gastrointestinal tract, which has the second highest incidence among gastrointestinal tumors. At present, due to the limitations of current CRC treatment strategies, there is an urgent need for developing more effective therapies. B7 family member H4 (B7-H4) is associated with the progression of a wide spectrum of cancers, but its functional role in CRC is unknown. The purpose of this study is to clarify the role of B7-H4 in CRC and the underlying mechanisms in controlling the progression of CRC. Our data showed that B7-H4 expression in CRC tissues and cell lines was significantly upregulated as compared with normal tissues and normal cell lines. High B7-H4 expression was correlated with a poor prognosis of CRC patients. B7-H4 overexpression promoted the proliferation and invasion of CRC cells, which could be suppressed by Wnt signaling inhibitor. In a mouse xenograft model, silencing B7-H4 suppressed tumor growth and epithelial–mesenchymal transition (EMT) of CRC cells. Collectively, our study demonstrated the oncogenic roles of B7-H4 in regulating the proliferation, EMT as well as the migration of CRC cells through Wnt signaling pathway. The heightened expression of B7-H4 could serve as a prognostic marker for CRC patients.

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“…Moreover, endometrial cancer is the most common gynecologic cancer, with an increasing incidence worldwide. Patients that are diagnosed at an early stage present good prognosis and high survival rates, although when diagnosed at a late stage they have poor prognosis, mostly caused by tumor metastasis, which has low survival rates and limited treatment options [6][7][8][9]. Thus, improved treatment options for women that already present cervical and endometrial cancer are still necessary.…”

Section: Introductionmentioning

confidence: 99%

Aptamer-Functionalized Gold Nanoparticles for Drug Delivery to Gynecological Carcinoma Cells

Lopes-Nunes

Agonia²,

Rosado

et al. 2021

Cancers

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Cervical cancer is one of the most common cancers and is one of the major cause of deaths in women, especially in underdeveloped countries. The patients are usually treated with surgery, radiotherapy, and chemotherapy. However, these treatments can cause several side effects and may lead to infertility. Another concerning gynecologic cancer is endometrial cancer, in which a high number of patients present a poor prognosis with low survival rates. AS1411, a DNA aptamer, increases anticancer therapeutic selectivity, and through its conjugation with gold nanoparticles (AS1411-AuNPs) it is possible to improve the anticancer effects. Therefore, AS1411-AuNPs are potential drug carriers for selectively delivering therapeutic drugs to cervical cancer. In this work, we used AS1411-AuNPs as a carrier for an acridine orange derivative (C8) or Imiquimod (IQ). The AS1411 aptamer was covalently bound to AuNPs, and each drug was associated via supramolecular assembly. The final nanoparticles presented suitable properties for pharmaceutical applications, such as small size, negative charge, and favorable drug release properties. Cellular uptake was characterized by confocal microscopy and flow cytometry, and effects on cellular viability were determined by MTT assay. The nanoparticles were then incorporated into a gel formulation of polyethylene glycol, suitable for topical application in the female genital tract. This gel showed promising tissue retention properties in Franz cells studies in the porcine vaginal epithelia. These findings suggest that the tested nanoparticles are promising drug carriers for cervical cancer therapy.

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Isoliquiritigenin Reverses Epithelial-Mesenchymal Transition Through Modulation of the TGF-β/Smad Signaling Pathway in Endometrial Cancer

Cited by 26 publications

References 47 publications

M2-Type Macrophages Induce Tregs Generation by Activating the TGF-β/Smad Signalling Pathway to Promote Colorectal Cancer Development

M2-Type Macrophages Induce Tregs Generation by Activating the TGF-β/Smad Signalling Pathway to Promote Colorectal Cancer Development

B7 family member H4 induces epithelial-mesenchymal transition and promotes the proliferation, migration and invasion of colorectal cancer cells

Aptamer-Functionalized Gold Nanoparticles for Drug Delivery to Gynecological Carcinoma Cells

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