Cellular and molecular mechanisms underlying alcohol-induced aggressiveness of breast cancer

Abstract

Breast cancer is a leading cause of morbidity and mortality in women. Both Epidemiological and experimental studies indicate a positive correlation between alcohol consumption and the risk of breast cancer. While alcohol exposure may promote the carcinogenesis or onset of breast cancer, it may as well enhance the progression and aggressiveness of existing mammary tumors. Recent progress in this line of research suggests that alcohol exposure is associated with invasive breast cancer and promotes the growth and metastasis of mammary tumors. There are multiple potential mechanisms involved in alcohol-stimulated progression and aggressiveness of breast cancer. Alcohol may increase the mobility of cancer cells by inducing cytoskeleton reorganization and enhancing the cancer cell invasion by causing degradation and reconstruction of the extracellular matrix (ECM). Moreover, alcohol may promote the epithelial-mesenchymal transition (EMT), a hallmark of malignancy, and impair endothelial integrity, thereby increasing the dissemination of breast cancer cells and facilitating metastasis. Furthermore, alcohol may stimulate tumor angiogenesis through the activation of cytokines and chemokines which promotes tumor growth. Additionally, alcohol may increase the cancer stem cell population which affects neoplastic cell behavior, aggressiveness, and the therapeutic response. Alcohol can be metabolized in the mammary tissues and breast cancer cells which produces reactive oxygen species (ROS), causing oxidative stress. Recent studies suggest that the epidermal growth factor receptor (EGFR) family, particularly ErbB2 (a member of this family), is involved in alcohol-mediated tumor promotion. Breast cancer cells or mammary epithelial cells over-expressing ErbB2 are more sensitive to alcohol’s tumor promoting effects. There is considerable cross-talk between oxidative stress and EGFR/ErbB2 signaling. This review further discusses how the interaction between oxidative stress and EGFR/ErbB2 signaling contributes to the cellular and molecular events associated with breast cancer aggressiveness. We also discuss the potential therapeutic approaches for cancer patients who drink alcoholic beverages.

Alcohol and Cancer Stem Cells

“…Experimental studies clearly demonstrate that alcohol alters the behavior of cancer cells and transforms them into more aggressive phenotypes [ 4 ]. For example, in breast cancer cells, alcohol increased mobility and invasive potential; it also promoted the epithelial-mesenchymal transition (EMT), a hallmark of malignancy, and impaired endothelial integrity, thereby increasing the dissemination of breast cancer cells and facilitating metastasis.…”

Silencing the expression of copine-III enhances the sensitivity of hepatocellular carcinoma cells to the molecular targeted agent sorafenib

“…Attenuating the stemness of cancer cells would also be a useful strategy to enhance their susceptibility to antitumor agents 41. Among the identified surface markers of CSCs in human cancers, EpCAM,42 CD133,43 or CD9044 may be associated with HCC 45,46. Therefore, it is valuable to examine whether copine-III would modulate the expression of markers of CSCs associated with HCC and the roles of copine-III regulation of HCC CSCs.…”

Risk factors related to breast cancer development

“…There are multiple cellular mechanisms, promoted by alcohol consumption whose consequence is enhancement in tumoral aggressiveness: • alcohol metabolism, which produces acetaldehyde, a toxic and carcinogenic substance with affinity to DNA and proteins; • production of reactive oxygen species, which may favor tumorigenesis based on the oxidation process (oxidative stress); • reduced absorption performance of important nutrients and vitamins; • increased serum estrogen levels; • reduced immune system performance 8,26,27 .…”

“…Exposure to alcohol can help in the promotion of carcinogenesis; even with the existing malignancy, consuming alcohol can contribute to enhance the progression and aggressiveness of existing tumors by promoting cell mobility, EMT and angiogenesis 25,27 . Furthermore, cancer stem-like cells (CSC) are directly influenced by alcohol consumption and may increase their population, which may result in different behaviors of the tumor mass, leading to different therapeutic responses 25,27 .…”