Highlights d EMT-derived breast cancer cells can differentiate into postmitotic adipocytes d Adipogenesis disconnects cancer cells from an invasive and oncogenic phenotype d EMT/MET transcription factors and TGF-b signaling regulate cancer adipogenesis d Adipogenesis-inducing drug combinations repress metastasis in preclinical models SUMMARY Cancer cell plasticity facilitates the development of therapy resistance and malignant progression. De-differentiation processes, such as an epithelial-mesenchymal transition (EMT), are known to enhance cellular plasticity.Here, we demonstrate that cancer cell plasticity can be exploited therapeutically by forcing the trans-differentiation of EMT-derived breast cancer cells into post-mitotic and functional adipocytes. Delineation of the molecular pathways underlying such trans-differentiation has motivated a combination therapy with MEK inhibitors and the anti-diabetic drug Rosiglitazone in various mouse models of murine and human breast cancer in vivo. This combination therapy provokes the conversion of invasive and disseminating cancer cells into post-mitotic adipocytes leading to the repression of primary tumor invasion and metastasis formation. SignificanceCancer cell plasticity and EMT are dynamic and can occur during different steps of cancer metastasis. We demonstrate that cellular plasticity acquired by EMT can be exploited to trans-differentiate breast cancer cells into post-mitotic and functional adipocytes. Notably, adipogenic differentiation therapy with a combination of Rosiglitazone and an MEK inhibitor efficiently inhibits cancer cell invasion, dissemination, and metastasis formation in various preclinical mouse models of breast cancer. The results underscore the pivotal role of cancer cell plasticity in malignant tumor progression and reveal the therapeutic potential that lies in the targeting of cellular plasticity, for example by forcing post-mitotic adipogenesis.

There is a high prevalence of nonalcoholic fatty liver among certain population in Shanghai, to which overweight and hyperlipidemia are closely relevant.

Recent experimental studies showed that the access resistance (AR) of a nanopore with a low thickness-todiameter aspect ratio plays an important role in particle translocation. The existing theories usually only consider the AR without the presence of particles in the pore systems. Based on the continuum model, we systematically investigate the current change caused by nanoparticle translocation in different nanopore configurations. From numerical results, an analytical model is proposed to estimate the influence of the AR on the resistive-pulse amplitude, i.e., the ratio of the AR to the pore resistance. The current change is first predicted by our model for nanoparticles and nanopores with a wide range of sizes at the neutral surface charge. Subsequently, the effect of surface charges is studied. The results show that resistive-pulse amplitude decreases with the increasing surface charge of the nanoparticle or the nanopore. We also find that the shape of the position-dependent resistive-pulse might be distorted significantly at low bulk concentration due to concentration polarization. This study provides a deep insight into the AR in particle-pore systems and could be useful in designing nanopore-based detection devices.

Head and neck squamous cell carcinoma (HNSCC) is one of the main malignant tumours affecting human health, mainly due to delayed diagnosis and high invasiveness. Extracellular vehicles (EVs) are membranous vesicles released by cells into the extracellular matrix that carry important signalling molecules and stably and widely exist in various body fluids, such as plasma, saliva, cerebrospinal fluid, breast milk, urine, semen, lymphatic fluid, synovial fluid, amniotic fluid, and sputum. EVs transport almost all types of bioactive molecules (DNA, mRNAs, microRNAs (miRNAs), proteins, metabolites, and even pharmacological compounds). These “cargoes” can act on recipient cells, reshaping the surrounding microenvironment and altering distant targets, ultimately affecting their biological behaviour. The extensive exploration of EVs has deepened our comprehensive understanding of HNSCC biology. In this review, we not only summarized the effect of HNSCC-derived EVs on the tumour microenvironment but also described the role of microenvironment-derived EVs in HNSCC and discussed how the “mutual dialogue” between the tumour and microenvironment mediates the growth, metastasis, angiogenesis, immune escape, and drug resistance of tumours. Finally, the clinical application of EVS in HNSCC was assessed.