Functional Implications of Cathelicidin Antimicrobial Protein in Breast Cancer and Tumor-Associated Macrophage Microenvironment

It is well-established that tumor-associated macrophages (TAMs) play an important role in breast cancer development. Accumulating evidence suggested that human cathelicidin antimicrobial protein (CAMP), which is mainly expressed in host defense cells such as macrophages, is crucial not only in combating microorganisms but also promoting tumor growth. Here we report the interaction of CAMP with TAMs in breast cancer. CAMP expression was upregulated in cancer tissues and in the circulation of breast cancer patients. Surgical removal of tumor decreased CAMP peptide serum level. Knockdown of CAMP decreased cell proliferation and migration/invasion ability in breast cancer cells. CAMP expression was altered during macrophage M1/M2 polarization and was expressed predominantly in M2 phenotype. In addition, breast cancer cells co-cultured with macrophages upregulated CAMP expression and also increased cancer cell viability. Xenograft tumors reduced significantly upon CAMP receptor antagonist treatment. Our data implicated that CAMP confers an oncogenic role in breast cancer and plays an important role in the tumor microenvironment between TAMs and breast cancer cells, and blocking the interaction between them would provide a novel therapeutic option for this malignant disease.

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Targeting PKM2 promotes chemosensitivity of breast cancer cells in vitro and in vivo

Cancer Biomarkers ◽

10.3233/cbm-210111 ◽

2021 ◽

pp. 1-10

Author(s):

Yu Wang ◽

Han Zhao ◽

Ping Zhao ◽

Xingang Wang

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Cancer Cells ◽

Cancer Patients ◽

Poor Prognosis ◽

Breast Cancer Cells ◽

Breast Cancer Patients ◽

Cancer Tissues

BACKGROUND: Pyruvate kinase M2 (PKM2) was overexpressed in many cancers, and high PKM2 expression was related with poor prognosis and chemoresistance. OBJECTIVE: We investigated the expression of PKM2 in breast cancer and analyzed the relation of PKM2 expression with chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated whether PKM2 could reverse chemoresistance in breast cancer cells in vitro and in vivo. METHODS: Immunohistochemistry (IHC) was performed in 130 surgical resected breast cancer tissues. 78 core needle biopsies were collected from breast cancer patients before neoadjuvant chemotherapy. The relation of PKM2 expression and multi-drug resistance to NAC was compared. The effect of PKM2 silencing or overexpression on Doxorubicin (DOX) sensitivity in the MCF-7 cells in vitro and in vivo was compared. RESULTS: PKM2 was intensively expressed in breast cancer tissues compared to adjacent normal tissues. In addition, high expression of PKM2 was associated with poor prognosis in breast cancer patients. The NAC patients with high PKM2 expression had short survival. PKM2 was an independent prognostic predictor for surgical resected breast cancer and NAC patients. High PKM2 expression was correlated with neoadjuvant treatment resistance. High PKM2 expression significantly distinguished chemoresistant patients from chemosensitive patients. In vitro and in vivo knockdown of PKM2 expression decreases the resistance to DOX in breast cancer cells in vitro and tumors in vivo. CONCLUSION: PKM2 expression was associated with chemoresistance of breast cancers, and could be used to predict the chemosensitivity. Furthermore, targeting PKM2 could reverse chemoresistance, which provides an effective treatment methods for patients with breast cancer.

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Echinacoside Suppresses the Progression of Breast Cancer by Downregulating the Expression of miR-4306 and miR-4508

Integrative Cancer Therapies ◽

10.1177/15347354211062639 ◽

2021 ◽

Vol 20 ◽

pp. 153473542110626

Author(s):

Peng Bian ◽

Chuan Liu ◽

Wei Hu ◽

Yu Ding ◽

Shusheng Qiu ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Antitumor Effect ◽

Underlying Mechanism ◽

Migration And Invasion ◽

Invasion And Migration ◽

Anticancer Effects ◽

And Migration ◽

Cancer Tissues

The main treatment of breast cancer includes surgical resection, radiotherapy, chemotherapy, endocrine therapy, and molecular targeted therapy, but the outcomes remain unsatisfactory. Previous studies demonstrated that echinacoside, microRNA (miRNA/miR)-4306 and miR-4508 were associated with lymph node metastasis, chemoresistance and self-renewal capability in breast cancer, but in-depth studies on the underlying mechanism of their anticancer effects have not been performed to date. In order to identify the role of miR-4306 and miR-4508, and the mechanism of the antitumor effect of echinacoside in breast cancer, the present study first examined the expression of miR-4306 and miR-4508 in breast cancer tissues to examine their possible role in the development of breast cancer, then evaluated the effect of echinacoside on the expression of miR-4306 and miR-4508 on the viability, apoptosis, cell cycle, migration, and invasion abilities of breast cancer cells to explore the anti-cancer effect of echinacoside and the involvement of miR-4306 and miR-4508. Finally, the breast cancer cells and mice bearing breast cancer xenografts were treated with echinacoside and inhibitors of miR-4508 or miR-4306 to confirm their role on the anticancer effect of echinacoside. The results showed that miR-4306 and miR-4508 were decreased in breast cancer tissues and cells. Echinacoside inhibited cell proliferation, invasion and migration, and promoted the apoptosis of breast cancer cells by downregulating the expression of miR-4306 and miR-4508. In conclusion, this is the first study to show the association between echinacoside and miRNAs in cancer. The present study elucidates an underlying molecular mechanism of the antitumor effect of echinacoside on breast cancer, and thus may contribute to preventive and therapeutic strategies for breast cancer.

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Abstract P3-06-11: TRIM39 is a poor prognostic factor for breast cancer patients and promotes proliferation and migration of breast cancer cells

10.1158/1538-7445.sabcs19-p3-06-11 ◽

2020 ◽

Author(s):

Takuya Ogura ◽

Kotaro Azuma ◽

Junichiro Sato ◽

Keiichi Kinowaki ◽

Kazuhiro Ikeda ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Factor ◽

Cancer Cells ◽

Cancer Patients ◽

Breast Cancer Cells ◽

Breast Cancer Patients ◽

Poor Prognostic Factor ◽

And Migration ◽

Proliferation And Migration

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MiR-16-5p inhibits breast cancer by reducing AKT3 to restrain NF-κB pathway

Bioscience Reports ◽

10.1042/bsr20191611 ◽

2019 ◽

Vol 39 (8) ◽

Cited By ~ 5

Author(s):

Liwei Ruan ◽

Xiaojun Qian

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cancer Patients ◽

Breast Cancer Cells ◽

Luciferase Reporter ◽

Breast Cancer Patients ◽

Lower Survival Rate ◽

Cause Of Deaths ◽

Cancer Tissues ◽

Cell Migration And Proliferation

Abstract Background: Breast cancer endangers the life of women and has become the major cause of deaths among them. MiRNAs are found to exert a regulatory effect on the migration, proliferation and apoptosis of breast cancer cells. This research aims at investigating the miR-16-5p expression and its effect on the pathogenesis of breast cancer. Methods: Their clinical data were analyzed with qRT-PCR. CCK8, EdU and Transwell was performed to explore the function of miR-16-5p in cell migration and proliferation of breast cancer cells. Dual-luciferase reporter assay, immunohistochemistry and Western blotting were carried out to explore the relation between miR-16-5p and AKT3. Results: It was discovered that miR-16-5p was lowly expressed in breast cancer patients. Meanwhile, breast cancer patients with under-expressed miR-16-5p had a lower survival rate than those with highly expressed miR-16-5p. Furthermore, decreased miR-16-5p in cell and animal models enhanced migration and proliferation of breast cancer cells, stimulated cell cycle and reduced cell apoptosis. Finally, we found miR-16-5p restrained the NF-κB pathway and decreased AKT3 gene, thereby suppressing the breast cancer development. Conclusion: It can be seen that miR-16-5p exhibits a low expression in breast cancer tissues, which can inhibit breast cancer by restraining the NF-κB pathway and elevating reducing AKT3.

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TNFRSF9 Suppressed the Progression of Breast Cancer via the p38MAPK/PAX6 Signaling Pathway

10.21203/rs.3.rs-1232265/v1 ◽

2022 ◽

Author(s):

Xun Zhu ◽

Xiaorong Liu ◽

Yehui Zhou ◽

Chenglin Qin

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Immune Modulation ◽

Breast Cancer Cells ◽

Cancer Drug ◽

The Novel ◽

Breast Cancer Patients ◽

Immunotherapy Target ◽

Cancer Tissues

Abstract Background Worldwide, Breast cancer is the most common cancer in females. Endocrine therapy can effectively treat 85% of breast cancer patients, but 15% of patients could only be treated with chemotherapy and surgery, and the prognosis is much worse. Immunotherapy is the novel treatment for breast cancer that PD-1 and CTLA-4 antibodies have shown evidence of immune modulation in breast cancer drug trials. Methods and Result In this study, we report that TNFRSF9 regulates the cell proliferation, invasion, and apoptosis of breast cancer cells through regulating the phosphorylation of p38, thus further regulate the expression of PAX6. In both breast cancer tissues and cell lines, the levels of TNFRSF9 are significantly decreased, and breast cancer cell development will be promoted with knockdown of TNFRSF9. Moreover, we identify that downregulation of TNFRSF9 can upregulate the phosphorylated p38 (p-p38) and PAX6. We further elucidate that p-p38 is essential for PAX6 expression that p38 phosphorylation inhibitor can reverse the upregulation of PAX6 and suppress cell proliferation, invasion, and promote apoptosis in breast cancer cells. Conclusions In summary, this study proposed a novel TNFRSF9/p38/PAX6 axis that contributes to tumor suppression, which suggests a potential immunotherapy target for breast cancer.

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Controllable Drug Delivery by Na+/K+ ATPase α1 Targeting Peptide Conjugated DSPE-PEG Nanocarriers for Breast Cancer

Technology in Cancer Research & Treatment ◽

10.1177/15330338211027898 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110278

Author(s):

Yayan Yang ◽

Qian Feng ◽

Chuanfeng Ding ◽

Wei Kang ◽

Xiufeng Xiao ◽

...

Keyword(s):

Breast Cancer ◽

Drug Delivery ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Click Reaction ◽

Chemotherapy Drugs ◽

Targeting Peptide ◽

And Migration

Although Epirubicin (EPI) is a commonly used anthracycline for the treatment of breast cancer in clinic, the serious side effects limit its long-term administration including myelosuppression and cardiomyopathy. Nanomedicines have been widely utilized as drug delivery vehicles to achieve precise targeting of breast cancer cells. Herein, we prepared a DSPE-PEG nanocarrier conjugated a peptide, which targeted the breast cancer overexpression protein Na+/K+ ATPase α1 (NKA-α1). The nanocarrier encapsulated the EPI and grafted with the NKA-α1 targeting peptide through the click reaction between maleimide and thiol groups. The EPI was slowly released from the nanocarrier after entering the breast cancer cells with the guidance of the targeting NKA-α1 peptide. The precise and controllable delivery and release of the EPI into the breast cancer cells dramatically inhibited the cells proliferation and migration in vitro and suppressed the tumor volume in vivo. These results demonstrate significant prospects for this nanocarrier as a promising platform for numerous chemotherapy drugs.

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Effect of mild hypothermia on breast cancer cells adhesion and migration

BioScience Trends ◽

10.5582/bst.2012.v6.6.313 ◽

2012 ◽

Cited By ~ 1

Author(s):

Zhang

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Mild Hypothermia ◽

And Migration

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lincRNA-RP11400K9.4 Regulates Cell Survival and Migration of Breast Cancer Cells

Cancer Genomics & Proteomics ◽

10.21873/cgp.20231 ◽

2020 ◽

Vol 17 (6) ◽

pp. 769-779

Author(s):

MIGUEL A. FERNÁNDEZ-ROJAS ◽

JORGE MELENDEZ-ZAJGLA ◽

VILMA MALDONADO LAGUNAS

Keyword(s):

Breast Cancer ◽

Cell Survival ◽

Cancer Cells ◽

Breast Cancer Cells ◽

And Migration

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ILF3-AS1 promotes cell proliferation and inhibits cell apoptosis of breast cancer by binding with miR-4429 to upregulate RAB14

Human & Experimental Toxicology ◽

10.1177/0960327121989422 ◽

2021 ◽

pp. 096032712198942

Author(s):

Xiaoxue Zhang ◽

Xianxin Xie ◽

Kuiran Gao ◽

Xiaoming Wu ◽

Yanwei Chen ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Breast Cancer Cell ◽

Cell Apoptosis ◽

Breast Cancer Cells ◽

Migration And Invasion ◽

Cancer Cell Proliferation ◽

Breast Cancer Cell Proliferation ◽

Cancer Tissues

As one of the leading causes of cancer-related deaths among women, breast cancer accounts for a 30% increase of incidence worldwide since 1970s. Recently, increasing studies have revealed that the long non-coding RNA ILF3-AS1 is involved in the progression of various cancers. Nevertheless, the role of ILF3-AS1 in breast cancer remains largely unknown. In the present study, we found that ILF3-AS1 was highly expressed in breast cancer tissues and cells. ILF3-AS1 silencing inhibited breast cancer cell proliferation, migration and invasion, and promoted cell apoptosis. ILF3-AS1 bound with miR-4429 in breast cancer cells. Moreover, RAB14 was a downstream target of miR-4429, and miR-4429 expression was negatively correlated with RAB14 or ILF3-AS1 expression in breast cancer tissues. The result of rescue experiments demonstrated that overexpression of RAB14 can reverse the inhibitory effect of ILF3-AS1 knockdown on breast cancer cell proliferation, migration and invasion. Overall, ILF3-AS1 promotes the malignant phenotypes of breast cancer cells by interacting with miR-4429 to regulate RAB14, which might offer a new insight into the underlying mechanism of breast cancer.

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