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Bone loss remains a major health concern for astronauts during space flight. Increased osteoclast activity is one of the main causes of bone loss in astronauts subjected to microgravity conditions. However, the underlying molecular mechanisms remain unclear. Microtubule actin crosslinking factor 1 (MACF1) has been implicated in the regulation of cytoskeletal distribution, cell migration, and cell differentiation. Our previous studies have shown that MACF1 promotes the differentiation of pre-osteoclasts. However, whether MACF1 regulates the migration and cytoskeletal arrangement of pre-osteoclasts under microgravity conditions has not yet been elucidated. In this study, we used a hind-limb unloading (HLU) mouse model and a random positioning machine (RPM) to simulate the effects of microgravity on pre-osteoclasts. In the HLU mouse model, the expression of MACF1 was upregulated in primary pre-osteoclasts of mice, accompanied by enhanced migration in vivo. Moreover, simulated microgravity using the RPM also promoted MACF1 expression and migration of pre-osteoclasts in vitro. Additionally, knockdown of MACF1 disrupted cytoskeletal arrangement (F-actin and microtubules) and further inhibited the migration of pre-osteoclasts via the RhoA/ROCK1 signaling pathway. We further demonstrated that knockdown of MACF1 disrupted the enhanced migration and cytoskeleton arrangement of pre-osteoclasts induced by simulated microgravity. These data demonstrate that MACF1 positively regulates the migration and cytoskeletal organization of pre-osteoclasts under simulated microgravity, suggesting that MACF1 may be a therapeutic target for the treatment of bone loss induced by microgravity. • MACF1 is a microgravity sensitive gene. • Simulated microgravity induced MACF1 expression and migration of pre-osteoclasts. • MACF1 knockdown attenuated the cytoskeleton arrangement of pre-osteoclasts. • MACF1 knockdown inhibited the migration via the RhoA/Rock1 pathway. • MACF1 knockdown prevented the migration and cytoskeleton arrangement of pre-osteoclasts induced by simulated microgravity. [ABSTRACT FROM AUTHOR]

• PEITC inhibits the invasion and migration of colorectal cancer cells. • PEITC suppresses the EMT of colorectal cancer cells. • PEITC blocks the TGF-β1/Smad signaling pathway and TGF-β1 induced EMT. • PEITC might serve as a novel therapeutic agent with potent anti-cancer effects. Tumor metastasis is the leading cause of death in patients with colorectal cancer (CRC), in which epithelial-mesenchymal transition(EMT) plays a vital role. However, the exact mechanisms of this process remain largely unknown. The aim of the present study was to determine the role of phenethyl isothiocyanate (PEITC) in CRC metastasis by regulating EMT. Wound healing assays and Transwell matrix assays were used to evaluate the potential of PEITC to inhibit CRC cells invasion and migration in vitro. Western blotting, light microscopy and immunofluorescence assays were used to detect the occurrence of EMT. Luciferase activity assay, real time-PCR and western blotting were used to investigate TGF-β1/Smad signaling activity. We observed that PEITC, an isothiocyanate compound from crucifer with chemopreventive potential, inhibited the invasion and migration of CRC cells. Moreover, we showed that PEITC regulated the EMT of CRC cells. Additionally, we demonstrated that PEITC blocked the activation of the TGF-β1/Smad pathway and significantly suppressed TGF-β1-induced EMT. Our results suggested that PEITC plays a crucial role in inhibiting the invasion and migration of CRC cells by regulating TGF-β1-induced EMT. The results of the present study provide a theoretical basis for the use of PEITC to treat CRC. [ABSTRACT FROM AUTHOR]