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Komiya, T.

Publications and source records attributed to Komiya, T..

4 recordsLinked to original sources

Dawn of segmented bilaterians unveiled by soft-bodied fossils in microbial pseudomorphs from the Basal Cambrian

It is estimated that the evolution of segmented bilaterians occurred during the Ediacaran, whereas most of their unambiguous body fossils did not appear until Cambrian Stage 3. This fossil gap hampers our understanding of the early history of body segmentation, which is a crucial evolutionary innovation for bilaterians. Trace fossils from the late Ediacaran and basal Cambrian suggest this gap is likely to represent a taphonomic bias, implying that the progenitors of segmented bilaterians that existed within this temporal span were hardly preserved. Here, we report a variety of segmented bilaterians from the lowermost Cambrian of South China. These fossils are preserved as microbial pseudomorphs, rather than as ordinary phosphatization. These findings demonstrate that microbial pseudomorphs represent a major pathway for the preservation of segmented bilaterians during this period, as well as an effective mechanism for overcoming the taphonomic bias that affects micro-animals with delicate, non-biomineralized bodies. Moreover, the newly described animals, among the earliest segmented bilaterians, reveal a high diversity of segmented bilaterians during Ediacaran-Cambrian transition, shedding new light on the evolution of body segmentation.

paleontology↗

M1C is a druggable target for NSCLC KRAS G12C mutant tumors resistant to KRAS inhibitors

Treatment of NSCLC KRAS G12C mutant tumors with the allele-selective sotorasib inhibitor is invariably associated with acquired resistance. The MUC1-encoded oncogenic M1C protein is necessary for self-renewal of NSCLC KRAS mutant cells. We report that treatment of NSCLC KRAS G12C cells with sotorasib induces M1C expression by a STAT1-dependent pathway. In turn, M1C drives sotorasib resistance by NF-{kappa}B-mediated induction of the epithelial-mesenchymal transition (EMT). Targeting M1C(R)NF-{kappa}B signaling (i) suppresses EMT, and (ii) reverses sotorasib resistance. Of translational relevance, treatment with a M1C antibody-drug conjugate (ADC) is effective against sotorasib-resistant NSCLC KRAS G12C cell line and patient-derived tumor xenografts. Clinically, targeted treatment of patients with NSCLC KRAS G12C tumors overexpressing MUC1 associates with decreases in overall survival. These findings identify M1C as a key effector of sotorasib resistance and as a target for treatment of patients with refractory NSCLC KRAS G12C mutant tumors.

cancer biology↗

Basal Cambrian soft-bodied segmented bilaterians preserved as microbial pseudomorphs

Before Cambrian Stage 3, unambiguous body fossils of segmented bilaterians were rare, severely hampering our understanding of the early history of such important animals. Here we report a variety of microfossils with quintessential features such as paired appendages, dorsoventral and anteroposterior differentiations from the basal Cambrian Fortunian of South China, representing the earliest known three-dimensional body fossils of segmented bilaterians. These fossils were all microbial pseudomorphs built up by secondarily phosphatized bacteria aggregations, testifying microbial pseudomorph could serve as a novel and important pathway to preserve tiny, fragile bilaterian progenitors. This finding unveils a diversified segmented bilaterian world at the very beginning of Cambrian and would arouse a more comprehensive perspective on the early evolution of bilaterian body plans.

paleontology↗

Muscle systems and motility of early animals highlighted by cnidarians from the basal Cambrian

Although fossil evidence suggest that various animal groups were able to move actively through their environment in the early stages of their evolution, virtually no direct information is available on the nature of their muscle systems. The origin of jellyfish swimming, for example, is of great concern to biologists. Exceptionally preserved muscles are described here in benthic peridermal olivooid medusozoans from the basal Cambrian of China (Kuanchuanpu Formation, ca. 535 Ma) that have direct equivalent in modern medusozoans. They consist of circular fibers distributed over the bell surface (subumbrella) and most probably have a myoepithelial origin. This is the oldest record of a muscle system in cnidarians and more generally in animals. This basic system was probably co-opted by younger early Cambrian jellyfish to develop capacities for the jet-propelled swimming within the water column. Additional lines of fossil evidence obtained from ecdysozoans (worms and panarthropods) show that the muscle systems of early animals underwent a rapid diversification through the early Cambrian and increased their capacity to colonize a wide range of habitats both within the water column and sediment at a critical time of their evolutionary radiation.

evolutionary biology↗