Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer / 中华医学杂志(英文版)

BACKGROUND@#Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a micro-barrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.@*METHODS@#The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models.@*RESULTS@#Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.@*CONCLUSIONS@#The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Advances in the study of the m6A methyltransferase METTL3 promoting bladder cancer progression via AFF4/NF-κB/MYC signaling network / 现代泌尿外科杂志

Bladder cancer (BCa) is one of the most common cancers in urology,whose pathogenesis is still unclear. Methyltransferase-like 3(METTL3) is the most important part of N6-methyladenosine methyltransferase complex (m6A MTC),which mediates the methylation of mRNA to regulate the stability and translation process of mRNA. Researches have shown that METTL3 can promote BCa development via AFF4/NF-κB/MYC signaling network,which involves many kinds of signaling molecules. In addition,METTL3 can affect the expressions of AFF4,NF-κB and MYC,so as to affect their downstream signaling pathways and finally promote the malignant progression of tumor.

Research advances in the minimally invasive treatment of benign prostatic obstruction / 现代泌尿外科杂志

The number of benign prostatic obstruction (BPO) patients in China is increasing, and patients tend to be younger and younger. The former "gold standard" scheme of transurethral resection of the prostate (TURP) is more suitable for patients with prostate volume ranging from 40 mL to 80 mL, which may lead to excessive resection in patients with small prostate volume and low efficiency in patients with large prostate volume. New minimally invasive techniques have been introduced,including prostate artery embolization, laser surgery (such as holmium, green, diode, and thulium), minimally invasive simple prostatectomy, transperineal laser ablation, prostatic urethral lift,and robot-assisted water jet ablation of the prostate. These methods are alternatives to TURP and increasingly used in the treatment of BPO. This article reviewed the advances in minimally invasive treatment of BPO.

Research advances of urinary cell-free DNA in the detection and therapy of bladder cancer / 中华泌尿外科杂志

Bladder cancer is a common malignancy in the genitourinary system and the current therapeutic approaches are unsatisfactory. Urinary cell-free DNA (ucf DNA) has the ability to give comprehensive and crucial information on cancer as it carries genetic messages from cells shedding directly into urine as well as transporting from circulation. The ucf DNA of patients with bladder cancer carries disease information, suggesting that ucf DNA may have the ability to detect, monitor, and prognosticate patients with bladder cancer. The ucf DNA analysis bridges the gap between current techniques and enhances diagnostic and detection capabilities, and has a very promising future in term of translation into clinical practice. This article reviewed the progress of clinical applications of ucf DNA in bladder cancer.