The role of epithelial-to-mesenchymal plasticity in ovarian cancer progression and therapy resistance

Ovarian cancer is the most lethal of all gynecologic malignancies and the eighth leading cause of cancer-related deaths among women worldwide. The main reasons for this poor prognosis are late diagnosis; when the disease is already in an advanced stage, and the frequent development of resistance to current chemotherapeutic regimens. Growing evidence demonstrates that apart from its role in ovarian cancer progression, epithelial-to-mesenchymal transition (EMT) can promote chemotherapy resistance. In this review, we will highlight the contribution of EMT to the distinct steps of ovarian cancer progression. In addition, we will review the different types of ovarian cancer resistance to therapy with particular attention to EMT-mediated mechanisms such as cell fate transitions, enhancement of cancer cell survival, and upregulation of genes related to drug resistance. Preclinical studies of anti-EMT therapies have yielded promising results. However, before anti-EMT therapies can be effectively implemented in clinical trials, more research is needed to elucidate the mechanisms leading to EMT-induced therapy resistance

LARP7 suppresses P-TEFb activity to inhibit breast cancer progression and metastasis.

Transcriptional elongation by RNA polymerase (Pol) II is essential for gene expression during cell growth and differentiation. The positive transcription elongation factor b (P-TEFb) stimulates transcriptional elongation by phosphorylating Pol II and antagonizing negative elongation factors. A reservoir of P-TEFb is sequestered in the inactive 7SK snRNP where 7SK snRNA and the La-related protein LARP7 are required for the integrity of this complex. Here, we show that P-TEFb activity is important for the epithelial-mesenchymal transition (EMT) and breast cancer progression. Decreased levels of LARP7 and 7SK snRNA redistribute P-TEFb to the transcriptionally active super elongation complex, resulting in P-TEFb activation and increased transcription of EMT transcription factors, including Slug, FOXC2, ZEB2, and Twist1, to promote breast cancer EMT, invasion, and metastasis. Our data provide the first demonstration that the transcription elongation machinery plays a key role in promoting breast cancer progression by directly controlling the expression of upstream EMT regulators

Autophagy and urothelial carcinoma of the bladder: A review.

The incidence of urothelial carcinoma of the urinary bladder (bladder cancer) remains high. While other solid organ malignancies have seen significant improvement in morbidity and mortality, there has been little change in bladder cancer mortality in the past few decades. The mortality is mainly driven by muscle invasive bladder cancer, but the cancer burden remains high even in nonmuscle invasive bladder cancer due to high recurrence rates and risk of progression. While apoptosis deregulation has long been an established pathway for cancer progression, nonapoptotic pathways have gained prominence of late. Recent research in the role of autophagy in other malignancies, including its role in treatment resistance, has led to greater interest in the role of autophagy in bladder cancer. Herein, we summarize the literature regarding the role of autophagy in bladder cancer progression and treatment resistance. We address it by systematically reviewing treatment modalities for nonmuscle invasive and muscle invasive bladder cancer