Olfactomedin-4 is a candidate biomarker of solid gastric, colorectal, pancreatic, head and neck, and prostate cancers

Olfactomedin-4 (OLFM4, OLM4) is a 72 kDa secreted glycoprotein belonging to the olfactomedin family. The OLFM4 gene expression is regulated by the transcription factors NF-kappa B and AP-1, and the OLM4 functions are poorly understood. OLM4 has been described as being able to interact with cell surface proteins such as lectins and concanavalin-A suggesting that one function of OLM4 is to regulate cell adhesion and migration. OLM4 is a marker for intestinal stem cells and is expressed at the bottom of the intestinal crypts. Expression of OLM4 during tumor development showed that OLM4 expression is increased in the early stages of tumor initiation. As OLM4 is a secreted protein, it is a prime candidate for biomarker research for tumor detection or progression. Levels of circulating OLM4 were significantly higher in patients with gastric, colorectal, and pancreatic cancers than in healthy subjects

Irinotecan treatment and senescence failure promote the emergence of more transformed and invasive cells that depend on anti-apoptotic Mcl-1.

Induction of senescence by chemotherapy was initially characterized as a suppressive response that prevents tumor cell proliferation. However, in response to treatment, it is not really known how cells can survive senescence and how irreversible this pathway is. In this study, we analyzed cell escape in response to irinotecan, a first line treatment used in colorectal cancer that induced senescence. We detected subpopulations of cells that adapted to chemotherapy and resumed proliferation. Survival led to the emergence of more transformed cells that induced tumor formation in mice and grew in low adhesion conditions. A significant amount of viable polyploid cells was also generated following irinotecan failure. Markers such as lgr5, CD44, CD133 and ALDH were downregulated in persistent clones, indicating that survival was not associated with an increase in cancer initiating cells. Importantly, malignant cells which resisted senescence relied on survival pathways induced by Mcl-1 signaling and to a lesser extent by Bcl-xL. Depletion of Mcl-1 increased irinotecan efficiency, induced the death of polyploid cells, prevented cell emergence and inhibited growth in low-adhesion conditions. We therefore propose that Mcl-1 targeting should be considered in the future to reduce senescence escape and to improve the treatment of irinotecan-refractory colorectal cancers

Plant neighbour identity and invasive pathogen infection affect associational resistance to an invasive gall wasp

Theory predicts that mixed forests are more resistant to native pests than pure forests (i.e. associational resistance) because of reduced host accessibility and increased top-down control by natural enemies. Yet, whether the same mechanisms also apply to invasive pests remains to be verified. We tested the hypothesis of associational resistance against the invasive Asian chestnut gall wasp (ACGW, Dryocosmus kuriphilus) by comparing ACGW infestation rates on chestnuts (Castanea sativa) in stands varying in species composition (chestnut alone or associated with oaks, pines or ashes). We investigated the effects of reduced chestnut density and frequency in mixed stands, as well as the effect of biotic interactions between ACGW, its parasitoids and the chestnut blight disease (caused by Cryphonectria parasitica). ACGW infestation rates were significantly lower in chestnut-oak and chestnut-ash mixtures than in pure chestnut stands and chestnut-pine mixtures. Infestation rate decreased with decreasing chestnut relative proportion. The composition of native parasitoid communities emerged from galls significantly differed between pure and mixed chestnut stands, but not the species richness or abundance of parasitoids. The abundance of the introduced parasitoid Torymus sinensis was not correlated with ACGW infestation rates and was independent of stand composition. Blight symptoms modified ACGW infestation rates with taller trees being preferred when they were asymptomatic but avoided when they presented blight disease damage. Our results suggest that conservation biological control based on tree species mixtures could contribute to reducing the damage of invasive forest pests