Serine synthesis pathway upregulated by E-cadherin is essential for the proliferation and metastasis of breast cancers.

The loss of E-cadherin (E-cad), an epithelial cell adhesion molecule, has been implicated in the epithelial-mesenchymal transition (EMT), promoting invasion and migration of cancer cells and, consequently, metastasis. However, recent studies have demonstrated that E-cad supports the survival and proliferation of metastatic cancer cells, suggesting that our understanding of E-cad in metastasis is far from comprehensive. Here, we report that E-cad upregulates the de novo serine synthesis pathway (SSP) in breast cancer cells. The SSP provides metabolic precursors for biosynthesis and resistance to oxidative stress, critically beneficial for E-cad-positive breast cancer cells to achieve faster tumor growth and more metastases. Inhibition of PHGDH, a rate-limiting enzyme in the SSP, significantly and specifically hampered the proliferation of E-cad-positive breast cancer cells and rendered them vulnerable to oxidative stress, inhibiting their metastatic potential. Our findings reveal that E-cad adhesion molecule significantly reprograms cellular metabolism, promoting tumor growth and metastasis of breast cancers.

Self-Propelled Janus Colloids in Shear Flow.

To fully harness the potential of artificial active colloids, investigation of their response to various external stimuli including external flow is of great interest. Therefore, in this study, we perform experiments on SiO2-Pt Janus particles suspended in an aqueous medium in a capillary subjected to different shear flow rates. Particles were propelled using varied H2O2 (fuel) concentrations. For a particular propulsion speed, with increasing shear flow, a continuous transition in the motion of active Janus particles (JPs) from the usual random active motion to preferential movement along the vorticity direction and then finally to migration along the flow was observed. This transition was accompanied by a significant decline in in-plane fluctuations of the particle trajectories. Another key observation is that the activity of JPs produces a delay in shear-induced rolling, which at moderate flow, allows the JPs to adopt a specific orientation, facilitating their migration along the vorticity direction. At higher flow rates, once shear flow overcomes the activity-induced resistance and initiates rolling, the probability of JPs adopting such preferred orientations reduces. Our analysis further revealed that these transitions are governed by a nondimensional quantity λ, which compares the relative strength of the shear-induced particle flow to the propulsion speed.