Clinical Evolution of Epithelial–Mesenchymal Transition in Human Carcinomas

Navas, Tony; Kinders, Robert J.; Lawrence, Scott M.; Ferry-Galow, Katherine V.; Borgel, Suzanne; Hollingshead, Melinda G.; Srivastava, Apurva K.; Alcoser, Sergio Y.; Makhlouf, Hala R.; Chuaqui, Rodrigo F.; Wilsker, Deborah; Konaté, Mariam M.; Miller, Sarah; Voth, Andrea Regier; Chen, Li; Vilimas, Tomas; Subramanian, Jyothi; Rubinstein, Larry; Kummar, Shivaani; Chen, Alice; Bottaro, Donald P.; Doroshow, James H.; Parchment, Ralph E.

doi:10.1158/0008-5472.can-18-3539

Cited by 78 publications

(71 citation statements)

References 65 publications

(69 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, BC cells can employ a variety of mechanisms to escape cell death induced by chemotherapeutic drugs. These mechanisms mainly include the efflux and inactivation of drugs 20 , activation of bypass signaling or prosurvival pathways, enhancement of DNA damage repair 21 , and induction of epithelial-mesenchymal transition (EMT) 22 and stem-like property 23 . Also, a large body of evidence demonstrated that the content of exosomes secreted by tumor cells changes in response to cellular stress induced by anticancer therapy, resulting in the transfer of drug-resistant phenotypes among tumor cells in BC [24][25][26] .…”

Section: Exosome and Chemoresistance In Bcmentioning

confidence: 99%

Exosomes and breast cancer drug resistance

et al. 2020

View full text Add to dashboard Cite

Drug resistance is a daunting challenge in the treatment of breast cancer (BC). Exosomes, as intercellular communicative vectors in the tumor microenvironment, play an important role in BC progression. With the in-depth understanding of tumor heterogeneity, an emerging role of exosomes in drug resistance has attracted extensive attention. The functional proteins or non-coding RNAs contained in exosomes secreted from tumor and stromal cells mediate drug resistance by regulating drug efflux and metabolism, pro-survival signaling, epithelial–mesenchymal transition, stem-like property, and tumor microenvironmental remodeling. In this review, we summarize the underlying associations between exosomes and drug resistance of BC and discuss the unique biogenesis of exosomes, the change of exosome cargo, and the pattern of release by BC cells in response to drug treatment. Moreover, we propose exosome as a candidate biomarker in predicting and monitoring the therapeutic drug response of BC and as a potential target or carrier to reverse the drug resistance of BC.

show abstract

Section: Exosome and Chemoresistance In Bcmentioning

confidence: 99%

Exosomes and breast cancer drug resistance

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Epithelial-to-mesenchymal transition (EMT) often precedes, and in model systems has been shown to promote, tumor invasiveness and metastasis [40]. Concurrent overexpression of TKs and a set of EMT TAs that they regulate was used as a proxy of oncogenic TK pathway activation in samples from the BCa TCGA dataset [21].…”

Section: Discussionmentioning

confidence: 99%

Autocrine Signaling by Receptor Tyrosine Kinases in Urothelial Carcinoma of the Bladder

Lee

Silva

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Comprehensive characterizations of bladder cancer (BCa) have established molecular phenotype classes with distinct alterations and survival trends. Extending these studies within the tyrosine kinase (TK) family to identify disease drivers could improve our use of TK inhibitors to treat specific patient groups or individuals. We examined the expression distribution of TKs as a class (n = 89) in The Cancer Genome Atlas (TCGA) muscle invasive BCa data set (n >400). Patient profiles of potentially oncogenic alterations (overexpression and/or amplification) clustered TKs into 3 groups; alterations of group 1 and 3 TKs were associated with significantly worse patient survival relative to those without alterations. Many TK pathways induce epithelial-to-mesenchymal transition (EMT), which promotes tumor invasiveness and metastasis. Overexpression and/or amplification among 9 EMT transcriptional activators occurred in 43% of TCGA cases. Co-occurring alterations of TKs and EMT transcriptional activators involved most group 1 TKs; 24% of these events were associated with significantly worse patient survival. Co-occurring alterations of receptor TKs and their cognate ligands occurred in 16% of TCGA cases and several BCa-derived cell lines. Suppression of GAS6, MST1 or CSF1, or their respective receptors (AXL, MST1R and CSF1R), in BCa cell lines was associated with decreased receptor activation, cell migration, cell proliferation and anchorage independent cell growth. These studies reveal the patterns and prevalence of potentially oncogenic TK pathway-related alterations in BCa and identify specific alterations associated with reduced BCa patient survival. Detection of these features in BCa patients could better inform TK inhibitor use and improve clinical outcomes.

show abstract

“…Recent clinical work also suggests that EMT contributes to drug resistance by increasing cancer stem cell (CSC) markers. Treatment of a patient with metastatic prostate cancer with the PARP inhibitor talazoparib increased NANOG, CD133, CD44v6, and ALDH1, which are CSC markers [44] . TGF-β1-induced EMT increases ALDH expression and leads to the generation of CSCs.…”

Section: The Role Of Emt In Tumour Immune Evasion and Drug Resistancementioning

confidence: 98%

Targeting epithelial-mesenchymal transition - an ongoing wild goose chase

Mokhamatam¹,

Irlapati²,

Dravida³

2020

JCMT

View full text Add to dashboard Cite

Epithelial-mesenchymal transition (EMT) is a natural phenomenon thatoccurs during embryodevelopment. It is a phenomenon involving the transition of adherence-dependent stationary epithelial cells to adherence-independent migratory mesenchymal cells. Tumours reactivate this machinery and evade anti-tumour immunity and inhibition by cancer-specific drugs. EMT harnesses complex crosstalk among cancer cell signalling pathways that make it difficult to tackle therapeutically, and it plays a pivotal role in cancer metastasis. Most screening platforms and approved drugs are limited by their applicability to epithelial cancers. There is a significant need for developing new strategies targeting metastatic cancers. Here, we review the challenges with the current methods of screening and available drugs for EMT and shed some light on the key essentials needed for next-generation drug discovery attempts.

show abstract

Clinical Evolution of Epithelial–Mesenchymal Transition in Human Carcinomas

Cited by 78 publications

References 65 publications

Exosomes and breast cancer drug resistance

Exosomes and breast cancer drug resistance

Autocrine Signaling by Receptor Tyrosine Kinases in Urothelial Carcinoma of the Bladder

Targeting epithelial-mesenchymal transition - an ongoing wild goose chase

Contact Info

Product

Resources

About