Benzo-[a]-pyrene induces FAK activation and cell migration in MDA-MB-231 breast cancer cells

Abstract

Benzo-[a]-pyrene (B[a]P) is a family member of polycyclic aromatic hydrocarbons and a widespread environmental pollutant. It is a mammary carcinogen in rodents and contributes to the development of human breast cancer. However, the signal transduction pathways induced by B[a]P and its role in breast cancer progression have not been studied in detail. Here, we demonstrate that B[a]P induces cell migration through a lipoxygenase- and Src-dependent pathway, as well as the activation of focal adhesion kinase, Src, and the extracellular signal-regulated kinase 2 in MDA-MB-231 breast cancer cells. However, B[a]P is not able to promote migration in the mammary nontumorigenic epithelial cells MCF12A. Moreover, B[a]P promotes an increase of αvβ3 integrin-cell surface levels and an increase of metalloproteinase (MMP)-2 and MMP-9 secretions. In summary, our findings demonstrate that B[a]P induces the activation of signal transduction pathways and biological processes involved in the invasion/metastasis process in MDA-MB-231 breast cancer cells.

Aryl hydrocarbon receptor-dependent up-regulation of the heterodimeric amino acid transporter LAT1 (SLC7A5)/CD98hc (SLC3A2) by diesel exhaust particle extract in human bronchial epithelial cells

“…PAHs (Lecureur et al, 2005;Castillo-Sanchez et al, 2013). This may be consistent with the hypothesis that DEPe only transiently induced FAK and ERK activity in BEAS-2B cells, as soon as a sufficient level of DEPe-mediated CD98hc induction was reached.…”

Effect of the PTEN gene on adhesion, invasion and metastasis of osteosarcoma cells

“…It has further been observed that PTEN has the potential to regulate the invasive behavior of tumor cells by affecting the expression and phosphorylation level of focal adhesion kinase (FAK) (27). The activation of FAK promotes the proliferation and invasion of tumor cells, which are crucial for cancer development and metastasis (28)(29)(30). In addition, FAK can increase secretion of the matrix metalloproteinases in tumor cells, including MMP-2 and MMP-9 (30,31).…”

“…The activation of FAK promotes the proliferation and invasion of tumor cells, which are crucial for cancer development and metastasis (28)(29)(30). In addition, FAK can increase secretion of the matrix metalloproteinases in tumor cells, including MMP-2 and MMP-9 (30,31). Therefore, the levels of the above proteins are significantly involving with the capabilities of malignant tumor cell invasion and metastasis through degradation of the extracellular matrix (ECM) (31,32).…”

Filling the gap between chemical carcinogenesis and the hallmarks of cancer: A temporal perspective

“…57 Recently, some studies provided mechanistic clues showing that BaP may contribute to lung cancer cell invasion and metastasis by upregulating proinflammatory chemokines (IL8, CCL-2, CCL-3) and the one of the master regulator of the epithelial-to-mesenchymal transition, Twist. 60 BaP treatment was also able to increase the metastatic potential of hepatocellular carcinoma cell lines in a mouse model, likely through an activation of both angiogenesis and NF-kB pathway. 60 BaP treatment was also able to increase the metastatic potential of hepatocellular carcinoma cell lines in a mouse model, likely through an activation of both angiogenesis and NF-kB pathway.…”

“…58,59 Moreover, BaP was able to induce cell migration in triple-negative breast cancer MDA-MB-231 cells through a lipoxygenase-and Src-dependent pathway, notably by increasing the secretion of metalloproteinase MMP-2 and MMP-9. 60 BaP treatment was also able to increase the metastatic potential of hepatocellular carcinoma cell lines in a mouse model, likely through an activation of both angiogenesis and NF-kB pathway. 51 In conclusion, BaP is able to promote cell migration and invasion, contributing to increase the metastatic potential of several epithelial cells in different experimental settings.…”