Background Uncontrolled growth in solid breast cancer generates mechanical compression that may drive the cancer cells into a more invasive phenotype, but little is known about how such compression affects the key events and corresponding regulatory mechanisms associated with invasion of breast cancer cells including cellular behaviors and matrix degradation. Results Here we show that compression enhanced invasion and matrix degradation of breast cancer cells. We also identified Piezo1 as the putative mechanosensitive cellular component that transmitted compression to not only enhance the invasive phenotype, but also induce calcium influx and downstream Src signaling. Furthermore, we demonstrated that Piezo1 was mainly localized in caveolae, and both Piezo1 expression and compression-enhanced invasive phenotype of the breast cancer cells were reduced when caveolar integrity was compromised by either knocking down caveolin1 expression or depleting cholesterol content. Conclusions Taken together, our data indicate that mechanical compression activates Piezo1 channels to mediate enhanced breast cancer cell invasion, which involves both cellular events and matrix degradation. This may be a critical mechanotransduction pathway during breast cancer metastasis, and thus potentially a novel therapeutic target for the disease.

Uncontrolled growth in solid tumor generates compressive stress that drives cancer cells into invasive phenotypes, but little is known about how such stress affects the invasion and matrix degradation of cancer cells and the underlying mechanisms.Here we show that compressive stress enhanced invasion, matrix degradation, and invadopodia formation of breast cancer cells. We further identified Piezo1 channels as the putative mechanosensitive cellular components that transmit the compression to induce calcium influx, which in turn triggers activation of RhoA, Src, FAK, and ERK signaling, as well as MMP-9 expression. Interestingly, for the first time we observed invadopodia with matrix degradation ability on the apical side of the cells, similar to those commonly observed at the cell's ventral side. Furthermore, we demonstrate that Piezo1 and caveolae were both involved in mediating the compressive stress-induced cancer cell invasive phenotype as Piezo1 and caveolae were often colocalized, and reduction of Cav-1 expression or disruption of caveolae with methyl-β-cyclodextrin led to not only reduced Piezo1 expression but also attenuation of the invasive phenotypes promoted by compressive stress. Taken together, our data indicate that mechanical compressive stress activates Piezo1 channels to mediate enhanced cancer cell invasion and matrix degradation that may be a critical mechanotransduction pathway during, and potentially a novel therapeutic target for, breast cancer metastasis.

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Tourist arrivals and tourism revenues have been extensively studied to evaluate international tourist flows, whereas the structure and evolution of these flows have received less attention. Based on international tourist arrival data from 221 countries/regions during the period 1995–2018, this study applies network analysis to explore the structure and evolution of international tourist flows, and the roles and functions of countries/regions in the international tourist flow network. The results of this study reveal that the network density of international tourist flows is increasing. Countries/regions in Europe, East Asia and North America generally occupy a significantly important position within the international tourist flow network, especially Germany and China. Those geographically close countries/regions demonstrate the same or similar roles and positions in international tourism. This study has significant implications for tourist destination management and marketing.