Retinoic acid signaling and bladder cancer: Epigenetic deregulation, therapy and beyond.

Retinoic acid (RA) signaling is a crucial developmental pathway involved in urothelium development, differentiation and regeneration. Deregulation of the RA signaling is highly implicated in several cancers, including bladder cancer, underlying the need to unravel the complete regulatory aspects of the retinoids in bladder tumorigenesis. Given the fact that RA receptors are transcription factors functioning at the chromatin level and act in close cooperation with chromatin modifiers, it is known that retinoids show their efficacy by changing the epigenome. Bladder cancer can be defined as a "disease of chromatin" with mutations identified in the genes involved in chromatin regulation in 80% of the patients. Therefore, a careful examination of the epigenetic backgrounds and the breakdown of the emerging and highly underexplored field of RA dependent regulation of the epigenome is essential to fully understand the retinoid-dependent effects on bladder cancer. With this motivation, in this review, we evaluate the role of RA signaling in bladder cancer with a focus on the regulatory and mutational aspects, emphasizing the deregulatory characteristics in bladder cancer and highlighting the potential treatment opportunities with the RA and derivatives alone or in combination with epigenetic drugs.

Retinoids and EZH2 inhibitors cooperate to orchestrate anti-oncogenic effects on bladder cancer cells.

The highly mutated nature of bladder cancers harboring mutations in chromatin regulatory genes opposing Polycomb-mediated repression highlights the importance of targeting EZH2 in bladder cancer. Furthermore, the critical role of the retinoic acid signaling pathway in the development and homeostasis of the urothelium, and the anti-oncogenic effects of retinoids are well established. Therefore, our aim is to simultaneously target EZH2 and retinoic acid signaling in bladder cancer to potentiate the therapeutic response. Here we report that this coordinated targeting strategy stimulates an anti-oncogenic profile, as reflected by inducing a synergistic reduction in cell viability that was associated with increased apoptosis and cell cycle arrest in a cooperative and orchestrated manner. This study characterized anti-oncogenic transcriptional reprogramming centered on the transcriptional regulator CHOP by stimulating the endoplasmic reticulum stress response. We further portrayed a molecular mechanism whereby EZH2 maintains H3K27me3-mediated repression of a subset of genes involved in unfolded protein responses, reflecting the molecular mechanism underlying this co-targeting strategy. These findings highlight the importance of co-targeting the EZH2 and retinoic acid pathway in bladder cancers and encourage the design of novel treatments employing retinoids coupled with EZH2 inhibitors in bladder carcinoma.

Bringing classes back into poverty discussions.

The 1980s saw a shift in the emphasis of discourse on poverty from production relations to consumption relations, with levels of consumption and purchasing power used to define poverty. Based on this concept, much of the research establishes absolute poverty lines or develops relative indicators to distinguish between "poor" and "non-poor." This paper makes the case that such poverty measurement, while useful for assessing trends over the long term or taking into account relative dynamics, distorts our knowledge of poverty by hiding its root causes and results in overly optimistic interpretations. These discussions also decontextualize poverty from its political and economic context by uncritically accepting and promoting neoliberal regime. Moreover, the article questions the meaning of the "eradication of poverty" and suggests that the nominal rise in PPP income obscures historical capitalist accumulation processes (such as dispossession, proletarianization and depeasantization). As a result, the study suggests to recenter the analysis on the material causes of poverty, which are rooted in the functioning of the capitalist system, its antagonistic character, and the class-based contradictions of production itself.