MUC5B silencing reduces chemo-resistance of MCF-7 breast tumor cells and impairs maturation of dendritic cells

Abstract

Abstract. Mucins participate in cancer progression by regulating cell growth, adhesion, signaling, apoptosis or chemo-resistance to drugs. The secreted mucin MUC5B, the major component of the respiratory tract mucus, is aberrantly expressed in breast cancer, where it could constitute a cancer biomarker. In this study we evaluated the role of MUC5B in breast cancer by gene silencing the MUC5B expression with short hairpin RNA on MCF-7 cells. We found that MUC5B-silenced MCF-7 cells have a reduced capacity to grow, adhere and form cell colonies. Interestingly, MUC5B knock-down increased the sensitivity to death induced by chemotherapeutic drugs. We also show that MUC5B silencing impaired LPS-maturation of DCs, and production of cytokines. Furthermore, MUC5B knock-down also influenced DC-differentiation and activation since it resulted in an upregulation of IL-1β, IL-6 and IL-10, cytokines that might be involved in cancer progression. Thus, MUC5B could enhance the production of LPS-induced cytokines, suggesting that the use of MUC5B-based cancer vaccines combined with DC-maturation stimuli, could favor the induction of an antitumor immune response.

Distinct signatures of lung cancer types: aberrant mucin O-glycosylation and compromised immune response

“…This gene could be targeted to slow down tumor growth and metastasis [104]. Moreover, MUC5B silencing was shown to reduce chemo-resistance of breast tumor cells [105], suggesting this as an interesting target also for LUAD, where we found MUC5B as one of the upregulated genes. Mucin expression and its link to chemotherapy resistance has been reported even more broadly in cancer [106].…”

The Diverse Roles of the Mucin Gene Cluster Located on Chromosome 11p15.5 in Colorectal Cancer

“…A regulatory linkage between dual-specificity phosphatase 28 (DUSP28) and MUC5B/MUC16 was reported in pancreatic cancer cells by a study to elucidate the underlying mechanism by which DUSP28 promotes the development of pancreatic cancer (Lee et al, 2016). The overexpression of the MUC5B gene was reported to lead to the aggressive behavior of breast cancer cells (Valque et al, 2012), and silencing the MUC5B gene efficiently recovered the sensitivity of breast cancer cells to chemotherapeutic drugs by impairing the maturation of dendritic cells and inducing an antitumor immune response (Garcia et al, 2016).…”

“…To understand the effect of abnormal expression of the MUC5B gene on the malignant biological behavior of cancer cells, Lahdaoui et al (2017) knockdown the expression of the MUC5B gene in the human gastric cancer cell line KATO-III and the colon cancer cell line LS174T and found that the downregulation of the MUC5B gene induced a decrease in cell proliferation and migration in vitro and in vivo, partially mediated by the Wnt/β-catenin pathway. In addition, Garcia et al (2016) used short hairpin RNA (shRNA) to knockdown the expression of the MUC5B gene in the breast cancer cell line MCF-7. The results showed that reducing the expression of the MUC5B gene could inhibit the cell adhesion, cell growth and clonogenic ability of MCF-7cells but did not increase apoptosis (Reynolds et al, 2019).…”

“…The abnormal expression of the MUC5B gene can also affect the resistance of cancer cells to chemotherapy drugs. Garcia et al (2016) also showed that MUC5B was associated with a worse response to chemotherapy and that reducing the expression of MUC5B increased chemosensitivity (Reynolds et al, 2019). Leteurtre et al (2004) found that HT29-5M12 cells, which mainly express the MUC5B gene, were resistant to chemotherapeutic drugs such as MTX and 5-FU.…”

Dendritic cells in lung immunopathology

“…Further, as well as their direct roles in pathology, some of these Th2-driven outcomes feedback to affect ongoing DC function. For example, the mucin Muc5B has been shown to influence DC maturation in the context of tumour cells [ 69 ], though more work is needed to determine how goblet cell hyperplasia and mucins influence DCs to shape allergic inflammation in the lung.…”