TBX3, a member of the ancient and evolutionary conserved T-box transcription factor family, is a critical developmental regulator of several structures including the heart, mammary glands, limbs and lungs. Indeed, mutations in the human TBX3 lead to ulnar mammary syndrome which is characterized by several clinical malformations including hypoplasia of the mammary and apocrine glands, defects of the upper limb, areola, dental structures, heart and genitalia. In contrast, TBX3 has no known function in adult tissues but is frequently overexpressed in a wide range of epithelial and mesenchymal derived cancers. This overexpression greatly impacts several hallmarks of cancer including bypass of senescence, apoptosis and anoikis, promotion of proliferation, tumour formation, angiogenesis, invasion and metastatic capabilities as well as cancer stem cell expansion. The debilitating consequences of having too little or too much TBX3 suggest that its expression levels need to be tightly regulated. While we have a reasonable understanding of the mutations that result in low levels of functional TBX3 during development, very little is known about the factors responsible for the overexpression of TBX3 in cancer. Furthermore, given the plethora of oncogenic processes that TBX3 impacts, it must be regulating several target genes but to date only a few have been identified and characterised. Interestingly, while there is compelling evidence to support oncogenic roles for TBX3, a few studies have indicated that it may also have tumour suppressor functions in certain contexts. Together, the diverse functional elasticity of TBX3 in development and cancer is thought to involve, in part, the protein partners that it interacts with and this area of research has recently received some attention. This review provides an insight into the significance of TBX3 in development and cancer and identifies research gaps that need to be explored to shed more light on this transcription factor.

The cytotoxic activities of extracts (50 μg/ml) from 48 fungal strains, recovered from sediments of Pecém's offshore port terminal (Northeast coast of Brazil), against HCT-116 colon cancer cell lines were investigated. The most promising extract was obtained from strain BRF082, identified as Dichotomomyces cejpii by phylogenetic analyses of partial RPB2 gene sequence. Thus, it was selected for bioassay-guided isolation of the cytotoxic compounds. Large-scale fermentation of BRF082 in potato dextrose broth, followed by chromatographic purification of the bioactive fractions from the liquid medium, yielded gliotoxin (4) and its derivatives acetylgliotoxin G (3), bis(dethio)bis(methylsulfanyl)gliotoxin (1), acetylgliotoxin (5), 6-acetylbis(dethio)bis(methylsulfanyl)gliotoxin (2), besides the quinazolinone alkaloid fiscalin B. All isolated compounds were tested for their cytotoxicities against the tumor cell lines HCT-116, revealing 4 and 3 as the most cytotoxic ones (IC50 0.41 and 1.06 μg/ml, resp.).

Metabolomic profiles were explored to understand environmental and taxonomic influences on the metabolism of two congeneric zoanthids, Palythoa caribaeorum and P. variabilis, collected across distinct geographical ranges. Integrated mass spectrometry data suggested the major influence of geographical location on chemical divergence when compared to species differentiation.

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The inherent value of nature is immeasurable. That being said, through bioprospection – the systematic search for functional products or processes from living organisms –, the oceans and marine life have emerged as a relevant source of biodiscoveries that hold significant economic worth. Particularly considering the pharmaceutical industry, an increasing number of natural molecules of marine origin have been making their way into pipelines and receiving approval for clinical use. Still, in its earliest days, this had become an extractivist practice, putting marine environments at risk and nearly driving species to extinction through over-collecting. While it is now well understood that exploration of the oceans' living resources must withstand a sustainable agenda, thus, protecting the environment from unnatural genetic losses, it was the developments towards achieving more efficient bioprospective strategies and non-destructive but feasible means to assure product supply that pushed for the greatest advances in this field. Herein, we present our assessment of this story by telling it through the 20-year journey – and few detours –we took in the chemical and pharmacological study of the ascidian Eudistoma vannamei, a species endemic to the northeast coast of Brazil that retains novel natural products with remarkable modes of action. Indeed, ascidians figure among the most pharmacologically talented marine organisms, having yielded the active principles of three new anticancer drugs, one of which is being considered for repositioning towards the treatment of Covid-19. Finally, we argue that emphasizing the unceasing biotechnological potential of marine biological diversity, exemplified herein by Brazilian ascidians, but certainly true worldwide for this and many other groups, would work in favor of raising awareness and supporting strategies to foster conservation of the oceans. Keywords: blue biotechnology, marine biodiversity, ascidians, bioproducts, innovation.