The resistance of cancer cells to therapy is responsible for the death of most patients with cancer¹. Epithelial-to-mesenchymal transition (EMT) has been associated with resistance to therapy in different cancer cells^2,3. However, the mechanisms by which EMT mediates resistance to therapy remain poorly understood. Here, using a mouse model of skin squamous cell carcinoma undergoing spontaneous EMT during tumorigenesis, we found that EMT tumour cells are highly resistant to a wide range of anti-cancer therapies both in vivo and in vitro. Using gain and loss of function studies in vitro and in vivo, we found that RHOJ—a small GTPase that is preferentially expressed in EMT cancer cells—controls resistance to therapy. Using genome-wide transcriptomic and proteomic profiling, we found that RHOJ regulates EMT-associated resistance to chemotherapy by enhancing the response to replicative stress and activating the DNA-damage response, enabling tumour cells to rapidly repair DNA lesions induced by chemotherapy. RHOJ interacts with proteins that regulate nuclear actin, and inhibition of actin polymerization sensitizes EMT tumour cells to chemotherapy-induced cell death in a RHOJ-dependent manner. Together, our study uncovers the role and the mechanisms through which RHOJ acts as a key regulator of EMT-associated resistance to chemotherapy.

Fertility preservation (FP) protocols in case of breast cancer (BC) include mature oocyte cryopreservation following letrozole associated controlled ovarian hyperstimulation (Let-COH). To date, the impact of Let-COH on the follicular microenvironment has been poorly investigated, although a high androgen/estrogen ratio was previously associated with low oocyte quality. In this prospective study, follicular fluid (FF) steroid levels (estradiol, testosterone, progesterone) and cumulus cell (CC) gene expression related to oocyte quality (HAS2, PTGS2, GREM1) were compared between 23 BC patients undergoing Let-COH for FP and 24 infertile patients undergoing conventional COH without letrozole. All patients underwent an antagonist COH cycle, and ovulation was triggered with hCG or GnRHa in both groups. FF estradiol levels were significantly lower while testosterone levels were significantly higher in the study group compared to controls irrespective of the trigger method. However, estradiol levels increased significantly with GnRHa triggering compared to hCG in the study group (median = 194.5 (95.4–438) vs 64.4 (43.8–152.4) ng/ml, respectively, p < 0.001), but not in the control group (median = 335.5 (177.5–466.7) vs 354 (179–511) ng/ml, respectively). After hCG trigger, Cumulus cell (CC) gene expression was lower in the study group compared to the control group, and difference was significant for PTGS2. Conversely, CC gene expression of PTGS2 and GREM1 was significantly higher in the study group compared to controls when ovulation was triggered with GnRHa. Let-COH triggered with hCG may negatively impact oocyte quality. However, ovulation triggering with GnRHa may improve the oocyte microenvironment and cumulus cell genes expression in Let-COH, suggesting a positive impact on oocyte quality in breast cancer patients. Clinicaltrials.gov - NCT02661932 , registered 25 January 2016, retrospectively registered.

Background and objectives: Several studies revealed clinical signs of stunting and rickets among rural populations of Tibet Autonomous Region (T.A.R.), and especially amid children. Further, these populations are affected by a bone disease named Kashin-Beck disease (KBD). However, little is known about the dietary status of this population. This survey aimed to assess the usual intakes of young Tibetan children living in rural areas around Lhasa for energy, water, and ten minerals and trace elements (Na, K, Ca, P, Mg, Fe, Zn, Cu, Mn, and Se) involved in bone metabolism. Design: A cross-sectional survey was designed. Totally, 250 pre-school children aged 3–5 years living in rural areas were enrolled. The 24-h food recall method was used to collect the intakes for two days, during two different seasons (September 2012 and April 2013). Because Tibetan foods are mainly derived from local agriculture and artisanal production, a combination of food composition tables was compiled, including specific and local food composition data. Results: The Chinese dietary recommended intakes are not met for most of the elements investigated. Intake of sodium is much too high, while usual intakes are too low for K, Ca, Zn, Cu, and Se. Bioavailability of Ca, Fe, and Zn may be of concern due to the high phytic acid content in the diet. Conclusion: These nutrient imbalances may impact growth and bone metabolism of young Tibetan children. The advantages of the implementation of food diversification programs are discussed as well as the relevance of supplements distribution.