<p>c-Src is required for hypoxia-induced metastasis-associated functions in prostate cancer cells</p>

Abstract

Background: Metastasis is the major cause of therapeutic failure in prostate cancer patients, and hypoxia has been shown to promote metastatic functions. However, whether Src family kinases (SFKs) can be upregulated under hypoxia is unclear. Materials and methods: In the current study, we evaluated the effects of hypoxia on cellular functions and activities of different SFK members (c-Src, Lyn, Fyn) in prostate cancer cells. Prostate cancer cell functions were determined in vitro including migration (wound-healing assay), invasion (Matrigel-based transwell assay) and clonogenic cell survival (colony formation assay). Protein expression was detected by Western blotting and gene knockdown was accomplished by siRNA transfection. Results: SRC , but not LYN and FYN , is associated with overall survival in prostate cancer patients, while all three phosphorylated proteins are highly expressed in tumors compared to normal tissues. Short-term hypoxic exposure significantly enhances cell migration, invasion, clonogenic survival, and consistently, c-Src phosphorylation in both PC-3ML and C4-2B cells. Knockdown of SRC , but not LYN or FYN , abolished hypoxia-induced functions. Finally, small molecule Src inhibitors strongly inhibited cell behaviors and c-Src activation under hypoxic conditions. Conclusion: Our data show that hypoxia is able to enhance metastatic-associated cell functions by activating c-Src in prostate cancer cells. Importantly, SFK inhibition by small molecule inhibitors was able to impair hypoxia-induced metastasis associated cell functions, suggesting a possible role of SFK inhibitors for prostate cancer treatment.

FYN promotes gastric cancer metastasis by activating STAT3-mediated epithelial-mesenchymal transition

“…Researchers found that hypoxia could induce prostate cancer cell metastasis in an SRC-dependent manner. Further, SRC knockdown successfully prevented the hypoxia-induced effects [ 31 ]. Another in vivo experiment supports evidence for the role of SRC in prostate cancer metastasis [ 32 ].…”

Src Family Kinases as Therapeutic Targets in Advanced Solid Tumors: What We Have Learned So Far

“…As well as in other solid tumors, hypoxia has been shown to support prostate cancer progression. In a hypoxic environment, Src activity was essential in promoting metastatic functions such as cell migration, invasion, and clonogenic survival in prostate cancer [100]. Lyn seems to play a non-redundant role in prostate cancer and Park et al suggested that Lyn is more important than Src in determining prostate cancer cell proliferation in primary tissue, while Src specific inhibition affects primarily cellular migration [101].…”

Biomaterials for Three-Dimensional Cell Culture: From Applications in Oncology to Nanotechnology

“…By virtue of their built-in bioactivity, they exhibited diverse applications in cellular biology [ 61 ]. They have been used in cancer invasion studies to assess the metastasis capabilities of cancer cells [ 62 ]. Matrigels were used in cell culture of human pluripotent stem cells (hPSCs) to understand the impact of the micro-environmental factors on cell differentiation [ 63 ], for cardiomyocytes as in vitro models of heart activity [ 64 ] and organoid production [ 65 ].…”