Implications of stemness-related signaling pathways in breast cancer response to therapy

Angeloni, Valentina; Tiberio, Paola; Appierto, Valentina; Daidone, Maria Grazia

doi:10.1016/j.semcancer.2014.08.004

Cited by 53 publications

(34 citation statements)

References 121 publications

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“…In addition, we found that AHNAK expression partly regulated the Wnt/β-catenin pathway. According to results from previous studies, the Wnt signalling pathway is one of the key signalling pathways in cancer [29–31]. It is generally known that changes in cell motility and tumour metastasis are commonly related to the Wnt/β-catenin pathway.…”

Section: Resultsmentioning

confidence: 99%

AHNAK suppresses tumour proliferation and invasion by targeting multiple pathways in triple-negative breast cancer

Chen

Wang

Dai

et al. 2017

J Exp Clin Cancer Res

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BackgroundAHNAK, also known as desmoyokin, is a giant protein with the molecular size of approximately 700 kDa and exerts diverse functions in different types of cancer.ResultsIn the present study, we demonstrated that AHNAK mRNA levels were down-regulated in 7 out of 8 human breast cancer cell lines, especially in triple - negative breast cancer (TNBC) cell lines. Moreover, in patients with TNBC, the expression of AHNAK gene was inversely correlated with the tumor status (P = 0.015), lymph node status (P < 0.001), lymph node (LN) infiltration (P < 0.001) and TNM stage (P < 0.001). Moreover, down-regulated AHNAK expression was considered an independent prognostic factor associated with the poor survival of patients with TNBC. Overexpression of AHNAK in two TNBC cell lines, MDA-MB-231 and BT549, suppressed the in vitro TNBC cell proliferation and colony formation, and inhibited the in vivo TNBC xenograft growth and lung metastasis. The tumor suppressing effect of AHNAK in TNBC was associated with the AKT/MAPK signaling pathway and Wnt/β-catenin pathway. Consistent results were observed when AHNAK was knockdown in BT20 and MDA-MB-435 cells.ConclusionsTaken together, our results suggest that AHNAK acts as a tumor suppressor that negatively regulates TNBC cell proliferation, TNBC xenograft growth and metastasis via different signaling pathways.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0522-4) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

AHNAK suppresses tumour proliferation and invasion by targeting multiple pathways in triple-negative breast cancer

Chen

Wang

Dai

et al. 2017

J Exp Clin Cancer Res

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“…As such, inhibiting one CSC subpopulation may lead to tumor reconstitution by the other CSC subpopulation. While targeting bulk and both CSC subpopulations is clearly desirable for effective TNBC treatment, mechanistic insights and therapeutic approaches remain elusive (Angeloni et al ., ).…”

Section: Introductionmentioning

confidence: 97%

Dual inhibition of Wnt and Yes‐associated protein signaling retards the growth of triple‐negative breast cancer in both mesenchymal and epithelial states

Sulaiman

McGarry

et al. 2018

Molecular Oncology

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Triple‐negative breast cancer (TNBC), the most refractory subtype of breast cancer to current treatments, accounts disproportionately for the majority of breast cancer‐related deaths. This is largely due to cancer plasticity and the development of cancer stem cells (CSCs). Recently, distinct yet interconvertible mesenchymal‐like and epithelial‐like states have been revealed in breast CSCs. Thus, strategies capable of simultaneously inhibiting bulk and CSC populations in both mesenchymal and epithelial states have yet to be developed. Wnt/β‐catenin and Hippo/YAP pathways are crucial in tumorigenesis, but importantly also possess tumor suppressor functions in certain contexts. One possibility is that TNBC cells in epithelial or mesenchymal state may differently affect Wnt/β‐catenin and Hippo/YAP signaling and CSC phenotypes. In this report, we found that YAP signaling and CD44high/CD24−/low CSCs were upregulated while Wnt/β‐catenin signaling and ALDH+ CSCs were downregulated in mesenchymal‐like TNBC cells, and vice versa in their epithelial‐like counterparts. Dual knockdown of YAP and Wnt/β‐catenin, but neither alone, was required for effective suppression of both CD44high/CD24−/low and ALDH+ CSC populations in mesenchymal and epithelial TNBC cells. These observations were confirmed with cultured tumor fragments prepared from patients with TNBC after treatment with Wnt inhibitor ICG‐001 and YAP inhibitor simvastatin. In addition, a clinical database showed that decreased gene expression of Wnt and YAP was positively correlated with decreased ALDH and CD44 expression in patients’ samples while increased patient survival. Furthermore, tumor growth of TNBC cells in either epithelial or mesenchymal state was retarded, and both CD44high/CD24−/low and ALDH+ CSC subpopulations were diminished in a human xenograft model after dual administration of ICG‐001 and simvastatin. Tumorigenicity was also hampered after secondary transplantation. These data suggest a new therapeutic strategy for TNBC via dual Wnt and YAP inhibition.

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“…Cancer stem cells share many mechanisms described for tissue-specific stem cells, but due to oncogenic deregulations these cells have evolved even drug-intoxicating and antioxidant systems that may contribute to tumor recurrence and enhanced resistance to chemo-and/or radiotherapy. Thus, drugs that inhibit breast cancer cell self-renewal and reduce chemoresistance offer great promise for breast cancer treatment [3]. [4].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Anti-tumor and Chemoresistance-lowering Effects of Pectolinarigenin from <i>Cirsium japonicum</i> Fisch ex DC in Breast Cancer

Lu¹,

Xu²,

Lu³

et al. 2016

Trop. J. Pharm Res

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Implications of stemness-related signaling pathways in breast cancer response to therapy

Cited by 53 publications

References 121 publications

AHNAK suppresses tumour proliferation and invasion by targeting multiple pathways in triple-negative breast cancer

AHNAK suppresses tumour proliferation and invasion by targeting multiple pathways in triple-negative breast cancer

Dual inhibition of Wnt and Yes‐associated protein signaling retards the growth of triple‐negative breast cancer in both mesenchymal and epithelial states

Evaluation of Anti-tumor and Chemoresistance-lowering Effects of Pectolinarigenin from <i>Cirsium japonicum</i> Fisch ex DC in Breast Cancer

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