Cell Reprogramming in Tumorigenesis and Its Therapeutic Implications for Breast Cancer

Chu, Pei‐Yi; Hou, Ming‐Feng; Lai, Ji-Ching; Chen, Long-Fong; Lin, Chang-Shen

doi:10.3390/ijms20081827

Cited by 14 publications

(9 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More specifically, the distinct cells of origin of BC subtypes are linked to specific genetic or epigenetic alterations following retro-or transdifferentiation which can mutually convert between basal and luminal cells. These events along intermediate mammary stem cell phenotypes suggest heterogeneous BC populations that are difficult to eliminate at the clinical level [49].…”

Section: Cell Plasticity As Basis Of Intratumoral Heterogeneity and Dmentioning

confidence: 99%

The Intimate Relationship among EMT, MET and TME: A T(ransdifferentiation) E(nhancing) M(ix) to Be Exploited for Therapeutic Purposes

Hass

Ohe

Ungefroren

2020

Cancers

View full text Add to dashboard Cite

Intratumoral heterogeneity is considered the major cause of drug unresponsiveness in cancer and accumulating evidence implicates non-mutational resistance mechanisms rather than genetic mutations in its development. These non-mutational processes are largely driven by phenotypic plasticity, which is defined as the ability of a cell to reprogram and change its identity (phenotype switching). Tumor cell plasticity is characterized by the reactivation of developmental programs that are closely correlated with the acquisition of cancer stem cell properties and an enhanced potential for retrodifferentiation or transdifferentiation. A well-studied mechanism of phenotypic plasticity is the epithelial-mesenchymal transition (EMT). Current evidence suggests a complex interplay between EMT, genetic and epigenetic alterations, and clues from the tumor microenvironment in cell reprogramming. A deeper understanding of the connections between stem cell, epithelial–mesenchymal, and tumor-associated reprogramming events is crucial to develop novel therapies that mitigate cell plasticity and minimize the evolution of tumor heterogeneity, and hence drug resistance. Alternatively, vulnerabilities exposed by tumor cells when residing in a plastic or stem-like state may be exploited therapeutically, i.e., by converting them into less aggressive or even postmitotic cells. Tumor cell plasticity thus presents a new paradigm for understanding a cancer’s resistance to therapy and deciphering its underlying mechanisms.

show abstract

Section: Cell Plasticity As Basis Of Intratumoral Heterogeneity and Dmentioning

confidence: 99%

The Intimate Relationship among EMT, MET and TME: A T(ransdifferentiation) E(nhancing) M(ix) to Be Exploited for Therapeutic Purposes

Hass

Ohe

Ungefroren

2020

Cancers

View full text Add to dashboard Cite

show abstract

“…As breast cancer can be categorized into various subtypes according to histopathological parameters or genomic signatures, and different subtypes exhibit varieties of cancer incidence, therapeutic response and prognosis [3][4][5], suggesting that it is of paramount importance to identify efficient diagnostic biomarkers and therapeutic targets for breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA TUSC8 inhibits breast cancer growth and metastasis via miR-190b-5p/MYLIP axis

Zhao

Zhou

Zhao

et al. 2020

Aging

View full text Add to dashboard Cite

The lncRNA tumor suppressor candidate 8 (TUSC8) plays a critical role in the development of several cancers. However, the biological functions and underlying molecular mechanisms of TUSC8 with respect to breast cancer remain largely unclear. Here, we found that TUSC8 was significantly down-regulated in breast cancer tissues and its high expression predicted better prognosis of breast cancer patients. Functionally, knock-down of TUSC8 drastically promoted the proliferation, migration and invasion of breast cancer cells in vitro and facilitated tumorigenicity and metastasis in vivo. Mechanistically, the results of luciferase reporter, RIP and RNA pulldown assays proved that TUSC8 functioned as molecular sponge for miR-190b-5p. Furthermore, we showed that TUSC8 served as a competing endogenous RNA (ceRNA) of myosin regulatory light chain interacting protein (MYLIP) through competitively binding with miR-190b-5p and suppressed breast cancer metastasis through regulating the expression of epithelial-mesenchymal transition (EMT) related markers. Clinically, the receiver operating characteristic curve (ROC) analyses revealed that the combination usage of TUSC8 and MYLIP might become novel promising diagnostic biomarkers for breast cancer. Taken together, these results suggested that TUSC8 inhibited breast cancer growth and metastasis via miR-190b-5p/MYLIP axis, providing us new insights into developing potential therapeutic targets for breast cancer patients.

show abstract

“…This is consistent with our finding that the ER-rich MCF-7 cells showed more proliferation than the ZR-75-1 cells, suggesting that cathepsin D may control ER-independent progression of breast cancer. As expected, cathepsin D silencing also stimulated the expression of ZO-1 and suppressed the level of N-cadherin, demonstrating that cathepsin D, as an independent marker of poor prognosis, could activate EMT, and in turn, induce cancer relapse and metastasis in luminal B subtype patients [ 29 ].…”

Section: Discussionmentioning

confidence: 64%

Characterizing the Relapse Potential in Different Luminal Subtypes of Breast Cancers with Functional Proteomics

Lin

Wang

Huang

et al. 2020

IJMS

View full text Add to dashboard Cite

Poor prognosis due to the high relapse and metastasis rates of breast cancer has been particularly linked to the luminal B subtype. The current study utilized MCF-7 and ZR-75-1 to investigate various luminal subtypes of breast cancers that have discrepant expressions in the estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). Understanding of the differential protein profiles and the associated pathways could help alleviate the malignance and promote the long-term survival rate of breast cancer patients. Functional proteome tools were applied to comprehensively delineate the global protein alterations that reflect the varieties of biological features between the two subtypes. In this study, a total of 11 proteins with significant and meaningful changes were identified. These protein targets including PRX2, CK19, nucleophosmin and cathepsin D were mostly involved in cell differentiation or proliferation. Particularly, cathepsin D was highly expressed in the luminal B subtype. Moreover, the level of cathepsin-D was also upregulated in the clinical metastatic tissues. Accordingly, the RNA interference-mediated silencing of cathepsin D stimulated ER expression but suppressed the level of HER2. The knockdown of cathepsin D enhanced the level of ZO-1 and a remarkable decrease in N-cadherin was also detected. Again, the matrix metalloproteinases (MMP) activity was impaired under the cathepsin D abolishment. Collectively, this study represented a modality to explore novel relationships in a proteome complex and highlighted the functional roles of cathepsin D in treatment options for different subtypes of breast cancer.

show abstract

Cell Reprogramming in Tumorigenesis and Its Therapeutic Implications for Breast Cancer

Cited by 14 publications

References 84 publications

The Intimate Relationship among EMT, MET and TME: A T(ransdifferentiation) E(nhancing) M(ix) to Be Exploited for Therapeutic Purposes

The Intimate Relationship among EMT, MET and TME: A T(ransdifferentiation) E(nhancing) M(ix) to Be Exploited for Therapeutic Purposes

Long non-coding RNA TUSC8 inhibits breast cancer growth and metastasis via miR-190b-5p/MYLIP axis

Characterizing the Relapse Potential in Different Luminal Subtypes of Breast Cancers with Functional Proteomics

Contact Info

Product

Resources

About