Biology subjects

Cetkovic, A.

Publications and source records attributed to Cetkovic, A..

3 recordsLinked to original sources

bioRxiv2026

MYC/MIZ1 suppression of lysosomal protein degradation drives immune evasion in pancreatic ductal adenocarcinoma

The MYC oncoprotein promotes immune evasion of pancreatic ductal adenocarcinoma (PDAC), but the underlying molecular mechanisms are not fully understood. Here we show that MYC protects PDAC tumors from CD4+ T cell-dependent elimination. Single cell sequencing shows that MYC suppression in tumor cells increases amino acid availability and broadly activates amino acid-responsive gene expression programs in immune cell populations. This occurs because MYC-driven uptake depletes free amino acids from tumor interstitial fluid and plasma, while MYC compromises macropinocytosis and autophagy, both of which depend on lysosomal protein degradation. MYC engages the POZ/BTB transcription factor MIZ1 to suppress lysosomal genes regulated by the TFE3/TFEB/MITF network or by free MIZ1, thereby inhibiting lysosomal protein degradation. An orthogonal genetic model enabling transient, selective inhibition of amino acid uptake in tumor cells recapitulates the effects of MYC depletion on amino acid levels in the tumor microenvironment and induces complete, CD4+ T cell-dependent tumor eradication with long-term survival. We propose that MYC-mediated, cell-autonomous disruption of lysosome function coupled to non-cell-autonomous protection from immune clearance allows MYC-low cells to benefit from MYC-high neighbors, such that intratumoral heterogeneity in MYC expression confers a selective advantage to the entire tumor. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/740267v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@140d2ccorg.highwire.dtl.DTLVardef@cf5f1borg.highwire.dtl.DTLVardef@6d132aorg.highwire.dtl.DTLVardef@10535e6_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2020

The hotter, the better: warmer winters boost the natural spread of an eastern Mediterranean bumblebee (Hymenoptera: Apidae: Bombus haematurus)

Range expansions of naturally spreading species are crucial for understanding how species interact with the environment and build their niche. Here, we studied the bumblebee Bombus haematurus Kriechbaumer, 1870, a species historically distributed in the eastern Mediterranean area which has very recently started expanding northwards into Central Europe. After updating the global distribution of this species, we investigated if niche shifts took place during this range expansion between colonized and historical areas. In addition, we have explored which climatic factors have favoured the natural range expansion of the species. Our results indicated that Bombus haematurus has colonized large territories in 7 European countries outside the historical area in the period from the 1980s to 2018, a natural expansion over an area that equals the 20% of the historical distribution. In addition, this bumblebee performs generalism in flower visitation and habitat use, although a preference for forested areas emerges. The land-use associated with the species in the colonized areas is similar to the historical distribution, indicating that no major niche shifts occurred during the spread. Furthermore, the component of climate change that favoured this colonization is the warming of winter temperatures and similar warming rates took place during both overwintering and queens emergence phases. These findings document a case of natural range expansion due to environmental change rather than due to niche shifts, and specifically they indicate that warmer winters are playing a major role in the process of natural colonization of new areas.

ecology↗

bioRxiv2019

A global synthesis reveals biodiversity-mediated benefits for crop production

Human land use threatens global biodiversity and compromises multiple ecosystem functions critical to food production. Whether crop yield-related ecosystem services can be maintained by few abundant species or rely on high richness remains unclear. Using a global database from 89 crop systems, we partition the relative importance of abundance and species richness for pollination, biological pest control and final yields in the context of on-going land-use change. Pollinator and enemy richness directly supported ecosystem services independent of abundance. Up to 50% of the negative effects of landscape simplification on ecosystem services was due to richness losses of service-providing organisms, with negative consequences for crop yields. Maintaining the biodiversity of ecosystem service providers is therefore vital to sustain the flow of key agroecosystem benefits to society.

ecology↗