scholarly journals Role of AXL in invasion and drug resistance of colon and breast cancer cells and its association with p53 alterations

2017 ◽  
Vol 23 (19) ◽  
pp. 3440 ◽  
Author(s):  
Wael M Abdel-Rahman ◽  
Noura A Al-khayyal ◽  
Vidhya A Nair ◽  
S R Aravind ◽  
Maha Saber-Ayad
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Breast Cancer Cells

PEAK1 promotes invasion and metastasis and confers drug resistance in breast cancer

2021 ◽  
Author(s):  
xingang wang ◽  
YAN ZHENG ◽  
YU WANG
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cell Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Multi Drug Resistance ◽  
Cancer Tissues

Abstract Background and AimsPseudopodium-enriched atypical kinase 1 (PEAK1) has reported to be upregulated in human malignancies and related with poor prognosis. Enhanced PEAK1 expression facilitates tumor cell survival, invasion, metastasis and chemoresistance. However, the role of PEAK1 in breast cancer is not clear. Here, we investigated the PEAK1 expression in breast cancer and analyzed its relation with clinicopathological status and chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated the role of PEAK1 on breast cancer cells in vitro and in vivo. MethodsImmunohistochemistry (IHC) was performed in 112 surgical resected breast cancer tissues. The associations between clinicopathological status, multi-drug resistance and PEAK1 expression were determined. Effect of PEAK1 overexpression or down-expression on proliferation, colony formation, invasion, migration, metastasis and Doxorubicin sensitivity in the MCF-7 cells in vitro and in vivo was detected. ResultsPEAK1 was overexpressed in breast cancer tissues and NAC -resistant breast cancer tissues. High PEAK1 expression was related with tumor size, high tumor grade, T stage, LN metastasis, recurrence, Ki-67 expression, Her-2 expression and multi-drug resistance. Targeting PEAK1 inhibited cell growth, invasion, metastasis and reversed chemoresistance to Doxorubicin in breast cancer cells in vitro and in vivo. ConclusionHigh PEAK1 expression was associated with invasion, metastasis and chemoresistance of breast cancers. Furthermore, targeting PEAK1 could inhibit cell growth and metastasis, and reverse chemoresistance in breast cancer cells, which provides an effective treatment strategies for breast cancer.

scholarly journals The role of p53-microRNA 200-Moesin axis in invasion and drug resistance of breast cancer cells

Tumor Biology ◽  
2017 ◽  
Vol 39 (9) ◽  
pp. 101042831771463 ◽  
Author(s):  
Farheen Alam ◽  
Fatima Mezhal ◽  
Hussain EL Hasasna ◽  
Vidhya A Nair ◽  
SR Aravind ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Morphological Changes ◽  
Mutant Cell ◽  
Migration And Invasion ◽  
Wild Type ◽  
Mesenchymal Transition

This study aimed to analyze the expression of microRNAs in relation to p53 status in breast cancer cells and to delineate the role of Moesin in this axis. We used three isogenic breast carcinoma cell lines MCF7 (with wild-type p53), 1001 (MCF7 with mutated p53), and MCF7-E6 (MCF7 in which p53 function was disrupted). MicroRNA expression was analyzed using microarray analysis and confirmed by real-time polymerase chain reaction. The 1001 clone with mutant p53 showed 22 upregulated and 25 downregulated microRNAs. The predicted targets of these 47 microRNAs were >700 human genes belonging to interesting functional groups such as stem cell development and maintenance. The most significantly downregulated microRNAs in the p53-mutant cell line were from the miR-200 family. We focused on miR-200c which targets many transcripts involved in epithelial-to-mesenchymal transition including Moesin. We found that Moesin was expressed in 1001 but not in its p53 wild-type parental MCF7 consistent with the observed mesenchymal features in the 1001, such as vimentin positivity, E-cadherin negativity, and ZEB1 positivity in addition to the morphological changes. After Moesin silencing, the p53-mutant cells 1001 reverted from mesenchymal-to-epithelial phenotype and showed subtle reduction in migration and invasion and loss of ZEB1 and SNAIL expression. Interestingly, Moesin silencing restored the 1001 sensitivity to Doxorubicin. These results indicate that loss of miR-200c, as a consequence of p53 mutation, can upregulate Moesin oncogene and thus promote carcinogenesis. Moesin may play a role in metastasis and drug resistance of breast cancer.

scholarly journals Extracellular Vesicles as Mediators of Therapy Resistance in the Breast Cancer Microenvironment

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 132
Author(s):  
Mark Samuels ◽  
Chiara Cilibrasi ◽  
Panagiotis Papanastasopoulos ◽  
Georgios Giamas
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Breast Cancer Cells ◽  
Therapy Resistance ◽  
Tumour Microenvironment ◽  
Cancer Microenvironment ◽  
Bidirectional Communication

Resistance to various therapies, including novel immunotherapies, poses a major challenge in the management of breast cancer and is the leading cause of treatment failure. Bidirectional communication between breast cancer cells and the tumour microenvironment is now known to be an important contributor to therapy resistance. Several studies have demonstrated that crosstalk with the tumour microenvironment through extracellular vesicles is an important mechanism employed by cancer cells that leads to drug resistance via changes in protein, lipid and nucleic acid cargoes. Moreover, the cargo content enables extracellular vesicles to be used as effective biomarkers for predicting response to treatments and as potential therapeutic targets. This review summarises the literature to date regarding the role of extracellular vesicles in promoting therapy resistance in breast cancer through communication with the tumour microenvironment.

scholarly journals Drug-resistant cancer cell-derived exosomal EphA2 promotes breast cancer metastasis via the EphA2-Ephrin A1 reverse signaling

2020 ◽  
Author(s):  
Zicong Gao ◽  
Xingxing Han ◽  
Yuying Zhu ◽  
He Zhang ◽  
Ran Tian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Resistant Cell ◽  
Migration And Invasion ◽  
Drug Resistant ◽  
Resistant Cells

Abstract Background: The failure of chemotherapy is accompanied by the emergence of drug resistance and tumor relapse. Tumor metastasis induced by drug resistance is a major challenge in successful cancer treatment. Nevertheless, the mechanisms underlying the pro-invasive and metastatic ability of drug resistance remain elusive. Exosome-mediated intercellular communications between cancer cells and stromal cells in tumor microenvironment are required for cancer initiation and progression. Recent reports have shown that communications between cancer cells also promote tumor aggression. However, little attention has been regarded on this aspect. In this study, we aimed to investigate the mechanisms of exosomes derived from drug-resistant cells in regulating the invasion and metastasis of sensitive breast cancer cells.Methods: Exosomes isolated from drug-resistant breast cancer cells and their parental cells were used to treat breast cancer cells, and then the migration and invasion abilities were examined. The tandem mass tag (TMT)-based quantitative proteomic method was carried out to identify key molecules that regulate cancer aggressiveness. Lentivirus-mediated shRNAs, overexpression, point mutation, truncation mutation, Western blotting, tumor xenograft mice models, and in vivo breast cancer metastatic models were used to investigate the functional role of EphA2 on the invasion and metastatic potential of breast cancer cells.Results: We demonstrated that drug-resistant cell-derived exosomes promoted the migration and invasion of sensitive breast cancer cells. Quantitative proteomic analysis showed that EphA2 was rich in exosomes from drug-resistant cells. Exosomal EphA2 conferred the invasive/metastatic phenotype transfer from drug-resistant cells to sensitive cells. In addition, we provided considerable evidence that exosomal EphA2 activated ERK1/2 signaling through the ligand Ephrin A1-dependent reverse pathway rather than the forward pathway, thereby promoting breast cancer progression. Conclusions: Our findings indicate the key functional role of exosomal EphA2 in the transmission of aggressive phenotype between cancer cells that do not rely on direct cell–cell contact. Our study also suggests that the increase of EphA2 in drug-resistant cell-derived exosomes may be an important mechanism of chemotherapy/drug resistance-induced breast cancer progression.

scholarly journals Matrix degradation and cell proliferation are coupled to promote invasion and escape from an engineered human breast microtumor

2021 ◽  
Vol 13 (1) ◽  
pp. 17-29
Author(s):  
Emann M Rabie ◽  
Sherry X Zhang ◽  
Andreas P Kourouklis ◽  
A Nihan Kilinc ◽  
Allison K Simi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Type I ◽  
Matrix Degradation ◽  
Human Breast ◽  
Rate Of Invasion

Abstract Metastasis, the leading cause of mortality in cancer patients, depends upon the ability of cancer cells to invade into the extracellular matrix that surrounds the primary tumor and to escape into the vasculature. To investigate the features of the microenvironment that regulate invasion and escape, we generated solid microtumors of MDA-MB-231 human breast carcinoma cells within gels of type I collagen. The microtumors were formed at defined distances adjacent to an empty cavity, which served as an artificial vessel into which the constituent tumor cells could escape. To define the relative contributions of matrix degradation and cell proliferation on invasion and escape, we used pharmacological approaches to block the activity of matrix metalloproteinases (MMPs) or to arrest the cell cycle. We found that blocking MMP activity prevents both invasion and escape of the breast cancer cells. Surprisingly, blocking proliferation increases the rate of invasion but has no effect on that of escape. We found that arresting the cell cycle increases the expression of MMPs, consistent with the increased rate of invasion. To gain additional insight into the role of cell proliferation in the invasion process, we generated microtumors from cells that express the fluorescent ubiquitination-based cell cycle indicator. We found that the cells that initiate invasions are preferentially quiescent, whereas cell proliferation is associated with the extension of invasions. These data suggest that matrix degradation and cell proliferation are coupled during the invasion and escape of human breast cancer cells and highlight the critical role of matrix proteolysis in governing tumor phenotype.

Sign in / Sign up

Export Citation Format

Share Document