The role of Hippo signal pathway in breast cancer metastasis

Wei, Chunli; Wang, Ying; Li, Xiangqi

doi:10.2147/ott.s157058

Cited by 68 publications

(50 citation statements)

References 74 publications

(77 reference statements)

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“…This pathway regulates cellular proliferation and apoptosis and has multiple family members that act as tumor suppressors (73). Activation of the HIPPO signaling pathway has also been shown to antagonize WNT signaling, whereas inhibition of HIPPO signaling (causing YAP hypophosphorylation and nuclear localization) can induce EMT (74,75). Downregulation of HIPPO signaling may therefore be involved in the increase in WNT signaling and EMT seen in the REM-134 RR cell line.…”

Section: Discussionmentioning

confidence: 99%

Comparative Analysis of the Development of Acquired Radioresistance in Canine and Human Mammary Cancer Cell Lines

et al. 2020

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Research using in vitro canine mammary cancer cell lines and naturally-occurring canine mammary tumors are not only fundamental models used to advance the understanding of cancer in veterinary patients, but are also regarded as excellent translational models of human breast cancer. Human breast cancer is commonly treated with radiotherapy; however, tumor response depends on both innate radiosensitivity and on tumor repopulation by cells that develop radioresistance. Comparative canine and human studies investigating the mechanisms of radioresistance may lead to novel cancer treatments that benefit both species. In this study, we developed a canine mammary cancer (REM-134) radioresistant (RR) cell line and investigated the cellular mechanisms related to the development of acquired radioresistance. We performed a comparative analysis of this resistant model with our previously developed human breast cancer radioresistant cell lines (MCF-7 RR, ZR-751 RR, and MDA-MB-231 RR), characterizing inherent differences through genetic, molecular, and cell biology approaches. RR cells demonstrated enhanced invasion/migration capabilities, with phenotypic evidence suggestive of epithelial-to-mesenchymal transition. Similarities were identified between the REM-134 RR, MCF-7 RR, and ZR-751 RR cell lines in relation to the pattern of expression of both epithelial and mesenchymal genes, in addition to WNT, PI3K, and MAPK pathway activation. Following the development of radioresistance, transcriptomic data indicated that parental MCF-7 and ZR-751 cell lines changed from a luminal A classification to basal/HER2-overexpressing (MCF-7 RR) and normallike/HER2-overexpressing (ZR-751 RR). These radioresistant subtypes were similar to the REM-134 and REM-134 RR cell lines, which were classified as HER2-overexpressing. To our knowledge, our study is the first to generate a canine mammary cancer RR cell line model and provide a comparative genetic and phenotypic analysis of the mechanisms of acquired radioresistance between canine and human cancer cell lines. We demonstrate that the cellular processes that occur with the development of acquired radioresistance Gray et al. Canine Radioresistant Mammary Cancer Model are similar between the human and canine cell lines; our results therefore suggest that the canine model is appropriate to study both human and canine radioresistant mammary cancers, and that treatment strategies used in human medicine may also be applicable to veterinary patients.

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Section: Discussionmentioning

confidence: 99%

Comparative Analysis of the Development of Acquired Radioresistance in Canine and Human Mammary Cancer Cell Lines

et al. 2020

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“…Hippo also controls organ size by inhibiting cell proliferation and promoting apoptosis (31). In turn, as described by Saeg and Anbalagan, the deregulation of Hippo signaling is believed to be responsible for the formation of Cancer Stem Cells (CSCs) in various types of cancer, including BC (32)(33). The proliferation of CSCs is known to be involved with activation of radioresistance.…”

Section: Discussionmentioning

confidence: 98%

Gene Expression Profiles Induced by High-dose Ionizing Radiation in MDA-MB-231 Triple-negative Breast Cancer Cell Line

Bravatà

Cammarata

Minafra

et al. 2019

Cancer Genomics Proteomics

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Background/Aim: Radiation therapy (RT) represents a therapeutic option in breast cancer (BC). Even if a great number of BC patients receive RT, not all of them report benefits, due to radioresistance that gets activated through several factors, such as the hormone receptor status. Herein, we analyzed the gene expression profiles (GEP) induced by RT in triple-negative BC (TNBC) MDA-MB-231, to study signalling networks involved in radioresistance. Materials and Methods: GEP of MDA-MB-231 BC cells treated with a high dose of radiation, went through cDNA microarray analysis. In addition, to examine the cellular effects induced by RT, analyses of morphology and clonogenic evaluation were also conducted. Results: A descriptive report of GEP and pathways induced by IR is reported from our microarray data. Moreover, the MDA-MB-231 Radioresistent Cell Fraction (RCF) selected, included specific molecules able to drive radioresistance. Conclusion: In summary, our data highlight, the RT response of TNBC MDA-MB-231 cell line at a transcriptional level, in terms of activating radioresistance in these cells, as a model of late-stage BC.

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“…First, metastasis is an essential hall marker of cancer and always leads to poor survival. [41][42][43] Numerous studies suggested that Tiam1 contributed to invasion and metastasis in various cancers, including osteosarcoma, 44 retinoblastoma, 45 gastric cancer, 46 CRC, [47][48][49][50][51] hepatocellular carcinoma, 25,52 breast cancer, 53 cholangiocarcinoma, 54 cervical cancer, 20 ovarian cancer, 55 nasopharyngeal cancer, 8,16 laryngeal cancer, 56 thyroid carcinoma, 57 nom-small cell lung cancer, 48 pancreatic cancer 6,58,59 and oral squamous cell carcinoma 27 Malliri et al reported that Tiam1 could facilitate E-cadherin-based adhesions between cancer cells in mouse intestinal tumors and human colon tumors, resulting in invasion and metastasis 60 Epithelial-mesenchymal transition (EMT) is a key process of enhancing cancer cell migration, invasion and metastasis. [28][29][30][31] Liu et al reported that Tiam1 overexpression could promote invasiveness and metastasis of thyroid carcinoma in vitro and in vivo by activating Wnt/EMT pathway 57 Similarly, Ding 6 and Yang et al 20 that Tiam1 overexpression could also boost invasion and metastasis of pancreatic cancer and cervical cancer by inducing EMT.…”

Section: Discussionmentioning

confidence: 99%

<p>High Tiam1 expression predicts positive lymphatic metastasis and worse survival in patients with malignant solid tumors: a systematic review and meta-analysis</p>

Yang

et al. 2019

OTT

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Background: Many studies have explored the prognostic value of T-cell lymphoma invasion and metastasis inducing factor 1 (Tiam1) and its association with lymphatic metastasis in malignant solid tumors, but the conclusions remain controversial. Therefore, we performed a meta-analysis to systematically assess the prognostic value of Tiam1 expression and its association with lymphatic metastasis in malignant solid tumors. Methods: We searched eligible studies in PubMed, Web of Science and EMBASE databases (from inception up to October 2018). The combined HR with 95% CI was used to estimate the prognostic value of Tiam1 expression. The correlation between Tiam1 expression and lymphatic metastasis was assessed using the combined odds ratio (OR) with 95% CI. Results: A total of 17 studies with 2,228 patients with solid tumors were included in this meta-analysis. The overall estimated results showed that high Tiam1 expression was significantly associated with shorter overall survival (HR= 2.08, 95% CI: 1.62-2.68, P<0.01), and disease-free survival (HR = 1.86, 95% CI: 1.49-2.32, P<0.01). Besides, we also found that there was a close relationship between high Tiam1 expression and positive lymphatic metastasis (OR=2.63; 95% CI: 1.79-3.84, P<0.01). Conclusion: High Tiam1 expression was significantly associated with shorter survival and positive lymphatic metastasis in patients with malignant solid tumors. Therefore, Tiam1 may be a promising prognostic biomarker and an effective therapeutic target for malignant solid tumors.

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The role of Hippo signal pathway in breast cancer metastasis

Cited by 68 publications

References 74 publications

Comparative Analysis of the Development of Acquired Radioresistance in Canine and Human Mammary Cancer Cell Lines

Comparative Analysis of the Development of Acquired Radioresistance in Canine and Human Mammary Cancer Cell Lines

Gene Expression Profiles Induced by High-dose Ionizing Radiation in MDA-MB-231 Triple-negative Breast Cancer Cell Line

<p>High Tiam1 expression predicts positive lymphatic metastasis and worse survival in patients with malignant solid tumors: a systematic review and meta-analysis</p>

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