DDR1 and MT1-MMP Expression Levels Are Determinant for Triggering BIK-Mediated Apoptosis by 3D Type I Collagen Matrix in Invasive Basal-Like Breast Carcinoma Cells

Type I collagen, the major components of breast interstitial stroma, is able to regulate breast carcinoma cell behavior. Discoidin domain receptor 1 (DDR1) is a type I collagen receptor playing a key role in this process. In fact, collagen/DDR1 axis is able to trigger the downregulation of cell proliferation and the activation of BIK-mediated apoptosis pathway. The aim of this review is to discuss the role of two important factors that regulate these processes. The first factor is the level of DDR1 expression. DDR1 is highly expressed in epithelial-like breast carcinoma cells, but poorly in basal-like ones. Moreover, DDR1 undergoes cleavage by MT1-MMP, which is highly expressed in basal-like breast carcinoma cells. The second factor is type I collagen remodeling since DDR1 activation depends on its fibrillar organization. Collagen remodeling is involved in the regulation of cell proliferation and apoptosis through age- and proteolysis-related modifications.

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Age-related modifications of type I collagen impair DDR1-induced apoptosis in non-invasive breast carcinoma cells

Cell Adhesion & Migration ◽

10.1080/19336918.2018.1472182 ◽

2018 ◽

pp. 1-13 ◽

Cited By ~ 6

Author(s):

Charles Saby ◽

Hassan Rammal ◽

Kevin Magnien ◽

Emilie Buache ◽

Sylvie Brassart-Pasco ◽

...

Keyword(s):

Breast Carcinoma ◽

Type I Collagen ◽

Carcinoma Cells ◽

Invasive Breast Carcinoma ◽

Type I ◽

Breast Carcinoma Cells ◽

Non Invasive ◽

Age Related ◽

Induced Apoptosis

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A comparison of spreading and motility behaviour of 8701-BC breast carcinoma cells on type I, I-trimer and type V collagen substrata. Evidence for a permissive effect of type I-trimer collagen on cell locomotion

Journal of Cell Science ◽

10.1242/jcs.100.1.179 ◽

1991 ◽

Vol 100 (1) ◽

pp. 179-185

Author(s):

C. Luparello ◽

P. Sheterline ◽

I. Pucci-Minafra ◽

S. Minafra

Keyword(s):

Breast Carcinoma ◽

Type I Collagen ◽

Tumour Cells ◽

Host Tissue ◽

Carcinoma Cells ◽

Type I ◽

Rhodamine Phalloidin ◽

Type V Collagen ◽

Breast Carcinoma Cells ◽

Type V

Ductal infiltrating carcinoma (d.i.c.) of human breast is a highly invasive neoplasm characterized by enhanced deposition of collagen. Paradoxically, enhanced collagen deposition is not correlated with inhibition of the migration of tumour cells into the host tissue. d.i.c. is characterized by the reappearance of ‘embryonic’ type I-trimer collagen and an increase in type V collagen content in the matrix. The effects of these two collagen types were compared with type I collagen as culture substrata on the spreading pattern, cytoskeletal organization and motile behaviour of 8701-BC breast carcinoma cells using rhodamine-phalloidin staining, a DNAase I-competition assay, scanning electron microscopy and time-lapse video-microscopy. Cells grown on type I collagen were stationary, showing a well-spread morphology and an extensive stress fibre pattern. Cells grown on type V collagen were also stationary, but displayed a poorly spread and elongated morphology. In contrast, cells grown on trimer collagen were motile and displayed a compact morphology and a reduced content of stress fibres. Both single-cell and group motility were detectable on trimer collagen substratum. These data are consistent with the existence of two opposite local signals, type I-trimer and type V collagens, which may confer a more or a less metastatic phenotype on breast carcinoma cells. Moreover, the synthesis of trimer collagen in d.i.c. is conceivably instrumental in providing new stromal pathways permitting tumour cells to infiltrate the host tissue.

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MT1-MMP protects breast carcinoma cells against type I collagen-induced apoptosis

Oncogene ◽

10.1038/onc.2011.249 ◽

2011 ◽

Vol 31 (4) ◽

pp. 480-493 ◽

Cited By ~ 40

Author(s):

E Maquoi ◽

D Assent ◽

J Detilleux ◽

C Pequeux ◽

J-M Foidart ◽

...

Keyword(s):

Breast Carcinoma ◽

Type I Collagen ◽

Carcinoma Cells ◽

Type I ◽

Breast Carcinoma Cells ◽

Induced Apoptosis

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Clinical effect of astragaloside IV on breast carcinoma cells based on MDR1: A randomised trial

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v20i11.12 ◽

2021 ◽

Vol 20 (11) ◽

pp. 2311-2316

Author(s):

Liangdong Chen ◽

Deqiang Zhuo ◽

Hongyin Yuan

Keyword(s):

Breast Carcinoma ◽

Western Blot ◽

Cell Invasion ◽

Clinical Effect ◽

Carcinoma Cells ◽

Astragaloside Iv ◽

Expression Levels ◽

Breast Carcinoma Cells ◽

Qrt Pcr ◽

Mcf 7

Purpose: To study the clinical effect of astragaloside IV on breast carcinoma cells (BCCs), and its potential mechanisms with respect to multiple drug resistance-1 (MDR1)Methods: The cytotoxicity of astragaloside IV to BCCs was determined using CCK-8 test, and values of its half inhibitory concentration (IC50) were determined. Transwell assay and flow cytometry were performed to determine the effect of astragaloside (13 μg/mL) on cell invasion and apoptosis. The contents of MDR1 mRNA in BC tissues and cells were determined using real-time quantitative polymerase chain reaction (qRT-PCR), while the protein expression levels of MDR1 in BC cells were determined using western blot assay.Results: The IC50 of astragaloside IV for MCF-7 and MDA-MB-231 BCCs were 12.57 μg/mL and 13.91 μg/mL, respectively. Transwell experiment showed significantly inhibited invasive capacity and enhanced apoptotic potential of the BCCs after astragaloside IV intervention. However, invasive capacities of the BCCs were markedly enhanced, while their apoptotic capacities were inhibited after transfection with si-MDR1, when compared with controls (p < 0.05). Results of qRT-PCR revealed that the mRNA content of MDR1 in BC tissues and cells (0.42±0.11) was significantly lower than that in normal tissues (0.95±0.18; p < 0.05). Results from western blot assay revealed that the relative expression levels of MDR1 protein were decreased, with values of 0.21±0.05, 0.32±0.07 and 0.74±0.15 for MCF-10A, MCF-7, MAD-MB-231 and MCF-10A, respectively (p < 0.05).Conclusion: Astragaloside IV regulates the metastasis and apoptosis of BCCs through regulation of MDR1. It also inhibits cell invasion but enhances the apoptosis of BC cells transfected with si-MDR1. These results highlight the prospects of the compound for the treatment of BC.

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Abstract 5107: DDR1 and MT1-MMP expression levels are major determinants of 3D type I collagen-induced apoptosis in basal-like breast carcinoma

10.1158/1538-7445.am2020-5107 ◽

2020 ◽

Author(s):

Charles Saby ◽

Guillaume Collin ◽

Maha Sinane ◽

Emilie Buache ◽

Laurence Van Gulick ◽

...

Keyword(s):

Breast Carcinoma ◽

Type I Collagen ◽

Type I ◽

Expression Levels ◽

Induced Apoptosis

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Nm23-H1 Metastasis Suppressor Expression Level Influences the Binding Properties, Stability, and Function of the Kinase Suppressor of Ras1 (KSR1) Erk Scaffold in Breast Carcinoma Cells

Molecular and Cellular Biology ◽

10.1128/mcb.25.4.1379-1388.2005 ◽

2005 ◽

Vol 25 (4) ◽

pp. 1379-1388 ◽

Cited By ~ 56

Author(s):

Massimiliano Salerno ◽

Diane Palmieri ◽

Amina Bouadis ◽

Douglas Halverson ◽

Patricia S. Steeg

Keyword(s):

Breast Carcinoma ◽

Cancer Therapeutics ◽

Carcinoma Cells ◽

Mitogen Activated Protein Kinase ◽

Metastasis Suppressor ◽

Binding Properties ◽

Altered Expression ◽

Expression Levels ◽

Breast Carcinoma Cells ◽

And Function

ABSTRACT Metastatic disease is a significant contributor to cancer patient mortality. We previously reported that the Kinase Suppressor of Ras1 (KSR1) scaffold protein for the Erk mitogen-activated protein kinase pathway coimmunoprecipitated the metastasis suppressor protein Nm23-H1. We now hypothesize that altered expression levels of Nm23-H1 influence the binding properties, stability, and function of the KSR1 scaffold. Increased coimmunoprecipitation of Hsp90 with KSR1 was observed in either stable or transient transfectants of nm23-H1 in MDA-MB-435 human breast carcinoma cells. Similar trends were also observed in the cytoplasmic and nuclear fractions of cells. Cells expressing high levels of Nm23-H1 exhibited increased KSR1 degradation in the presence of either cycloheximide or an Hsp90-directed drug currently in clinical trial, 17-allylamino-17-demethoxygeldanamycin (17-AAG). In agreement with KSR1 degradation data, high-Nm23-H1-expression cells were preferentially inhibited in anchorage-independent colonization assays by 17-AAG. KSR1 scaffold binding patterns are dynamic in both the cytoplasmic and nuclear compartments, modulated by metastasis suppressor expression. Metastasis suppressor expression levels can impact traditional signaling pathways, such as the Erk pathway, resulting in altered tumor cell sensitivity to cancer therapeutics.

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