DIS3L2 knockdown impairs key oncogenic properties of colorectal cancer cells via the mTOR signaling pathway.

DIS3L2 degrades different types of RNAs in an exosome-independent manner including mRNAs and several types of non-coding RNAs. DIS3L2-mediated degradation is preceded by the addition of nontemplated uridines at the 3'end of its targets by the terminal uridylyl transferases 4 and 7. Most of the literature that concerns DIS3L2 characterizes its involvement in several RNA degradation pathways, however, there is some evidence that its dysregulated activity may contribute to cancer development. In the present study, we characterize the role of DIS3L2 in human colorectal cancer (CRC). Using the public RNA datasets from The Cancer Genome Atlas (TCGA), we found higher DIS3L2 mRNA levels in CRC tissues versus normal colonic samples as well as worse prognosis in patients with high DIS3L2 expression. In addition, our RNA deep-sequencing data revealed that knockdown (KD) of DIS3L2 induces a strong transcriptomic disturbance in SW480 CRC cells. Moreover, gene ontology (GO) analysis of significant upregulated transcripts displays enrichment in mRNAs encoding proteins involved in cell cycle regulation and cancer-related pathways, which guided us to evaluate which specific hallmarks of cancer are differentially regulated by DIS3L2. To do so, we employed four CRC cell lines (HCT116, SW480, Caco-2 and HT-29) differing in their mutational background and oncogenicity. We demonstrate that depletion of DIS3L2 results in reduced cell viability of highly oncogenic SW480 and HCT116 CRC cells, but had little or no impact in the more differentiated Caco-2 and HT-29 cells. Remarkably, the mTOR signaling pathway, crucial for cell survival and growth, is downregulated after DIS3L2 KD, whereas AZGP1, an mTOR pathway inhibitor, is upregulated. Furthermore, our results indicate that depletion of DIS3L2 disturbs metastasis-associated properties, such as cell migration and invasion, only in highly oncogenic CRC cells. Our work reveals for the first time a role for DIS3L2 in sustaining CRC cell proliferation and provides evidence that this ribonuclease is required to support the viability and invasive behavior of dedifferentiated CRC cells.

Molecular survey of potentially pathogenic microorganisms in ticks collected from coatis (Nasua nasua) in Iguaçu National Park, Atlantic Forest biome, southern Brazil.

Human contact with wild animals in synanthropic habits is often mediated by arthropod vectors such as ticks. This is an important method of spreading infectious agents that pose a risk to human health. Thus, this study aimed to molecularly detect Ehrlichia spp., Anaplasma spp., Borrelia spp., and protozoa of the order Piroplasmida in ticks collected from coatis of Iguaçu National Park (PNI), Paraná, Brazil. This study involved 553 ticks DNA, including Amblyomma spp. larvae, Haemaphysalis juxtakochi nymphs, Amblyomma brasiliense, Amblyomma coelebs, and adults of Amblyomma ovale. The DNA extracted from each sample was subjected to polymerase chain reaction (PCR) targeting the genes 23S rRNA for the Anaplasmataceae family, 16S rRNA for Anaplasma spp., dsb for Ehrlichia spp., flaB, 16S rRNA, hpt, and glpQ for Borrelia spp., and 18S rRNA for Piroplasmid protozoans. DNA from Anaplasma sp. was detected in ticks of the species A. coelebs (4/553); Borrelia sp. DNA was detected in A. coelebs (3/553), A. ovale (1/553), and Amblyomma larvae (1/553); and Theileria sp. was detected in A. coelebs (2/553). All tested samples were negative for Ehrlichia spp. Our study constitutes the newest report in South America of these microorganisms, which remain poorly studied.

A Solution to Prevent and Minimize the Consequences of Accidents with Farm Tractors in the Context of Mountainous Regions with Low Population Density.

Farm tractors have become a key part of daily routine agriculture, converting complex and time-consuming tasks into tasks that are easier to perform and less dependent on human labor, contributing directly to increasing the economic value generated by this activity sector, either by increasing the productivity or by making certain agricultural crops viable, which otherwise would not be sustainable. However, despite all the advantages, accidents with this type of equipment are common, often with critical and sometimes fatal consequences. The evolution of safety requirements of these machines has occurred at a good level; however, a significant part of the agricultural tractors in use are older models that do not have such solutions. Even in the new models, which contain such solutions, these are not always correctly used, and it is even common that they are turned off or simply not used at all. It is therefore natural that accidents continue to occur, a situation that is aggravated by other factors. Lack of situational awareness of the operators, which can result from advanced age, inadequate training, reduced sensitivity/respect for safety rules, or working on irregular terrain like mountainous areas, contribute to high-risk contexts that end in the loss of human life. The consequences of such accidents are clearly aggravated by the time it takes to assist the victims-either because accidents are simply not identified/reported immediately, or by the time it takes to locate and provide help to the victims. This is a scenario that is more common in mountainous regions and regions with low population density. The current paper, using NB-IoT, a set of sensors, and a web application, presents a conceptual toolset conceived to prevent accidents and minimize consequences (human and material) that can be applied to old and new farm tractors. The development was carried out taking the characterization of the farmers and the land in the region in which the authors' research institution is located into account, which has the highest rate of fatal accidents with agricultural tractors in the country; it is a region of mountainous with a very low population density.

Targeting Cancer by Using Nanoparticles to Modulate RHO GTPase Signaling.

Functionalized nanomaterials have recently been introduced as efficient vehicles for targeted delivery of drugs and other tailored molecules to cancer cells. They emerge as new opportunities for addressing particular challenging targets such as RHO guanosine triphosphatases (GTPases), a group of signaling molecules involved in the progression of a variety of tumor types. RHO GTPases comprise a subfamily of the Ras superfamily of small GTPases. They are best known for their role in cell migration through the remodeling of the actin cytoskeleton. However, they are also key regulators of a broad number of cellular functions, ranging from proliferation to cell adhesion and differentiation. Not surprisingly, their dysregulation has been implicated in the development and progression of many types of cancer. The RHO GTPase subfamily includes 20 members that can be further separated into typical and atypical RHO GTPases. The typical RHO family members include the classical RHOA, RAC1 and CDC42 proteins, which cycle between an active GTP-bound and inactive GDP-bound conformation, under the coordinated action of three types of regulators: GEFs, GAPs and GDIs. Atypical RHO family members have small changes in key residues that alter their regulatory mechanisms. Nevertheless, both typical and atypical RHO GTPases contribute to cancer progression but, in contrast to Ras proteins, very few mutations have been found in tumors. In most cancers, it is the expression level and/or activity of RHO GTPases that is dysregulated. RHO GTPase signaling has thus long been seen as an attractive target for cancer treatment but their ubiquity and the lack of isoform-specific drugs have posed significant obstacles to the development of viable therapeutic strategies. Based on the success of recent nanomedicine approaches, this chapter reviews representative studies of how functionalized nanoparticles can be designed to target tumor-specific molecules and directly or indirectly modulate the expression and/or activity of particular RHO GTPases in cancer cells.

Sectoral connectedness: New evidence from US stock market during COVID-19 pandemics.

We examine volatility connectedness of 11 sectoral indices in the US using daily data from January 01, 2013 to December 31, 2020. We employ the connectedness measures of Diebold and Yilmaz (2009, 2012, 2014), unveiling changes in sectoral connectedness and stylized facts regarding specific sectors during the COVID-19 pandemic. Among several results, we find extraordinary increase in total connectedness, from early stages of international spread to the end of July 2020; some relevant changes in the pairwise connections between sectors, especially among the originally stronger ones. However, in a total net connectedness perspective, there is little evidence of structural changes.

External validity of type 2 diabetes clinical trials on cardiovascular outcomes for a multimorbid population.

AIM: To investigate the external validity of recent antihyperglycaemic trials evaluating cardiovascular outcomes in a multimorbid population. MATERIALS AND METHODS: Selection criteria of 15 randomized controlled trials from the 2020 American Diabetes Association Standard of Care statement were applied in a stepwise manner to tertiary care patients with type 2 diabetes. Primary outcomes were the number of patients eligible per individual trial and for the aggregate of trials. Secondary outcomes included patient predictors of trial eligibility. RESULTS: Of 1059 patients, the mean (SD) age was 66 (10.74) years, the median (IQR) Charlson index was 2 (2, 3) and 458 (43%) had documented cardiovascular disease. The median (IQR) number of patients included in individual trials was 263 (174.25-308.75) and 795 (75.1%) of them were eligible for at least one trial. Among those 264 ineligible, 127 (48.1%) had an HbA1c level of 7% or less and no cardiovascular disease; 53.5% and 34.4% of the patients were eligible for two and three different classes of drugs, respectively. The strongest predictor of trial eligibility was cardiovascular disease (risk ratio 2.17, 95% CI 2.01-2.35). CONCLUSIONS: A considerable proportion of multimorbid patients would be eligible for recent antihyperglycaemic trials. This positive finding can be attributed to development guidance in diabetes trials and the different approach we took, in which we evaluated inclusion by trials as an aggregate.

A SYK/SHC1 pathway regulates the amount of CFTR in the plasma membrane.

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause the recessive genetic disease cystic fibrosis, where the chloride transport across the apical membrane of epithelial cells mediated by the CFTR protein is impaired. CFTR protein trafficking to the plasma membrane (PM) is the result of a complex interplay between the secretory and membrane recycling pathways that control the number of channels present at the membrane. In addition, the ion transport activity of CFTR at the PM is modulated through post-translational protein modifications. Previously we described that spleen tyrosine kinase (SYK) phosphorylates a specific tyrosine residue in the nucleotide-binding domain 1 domain and this modification can regulate the PM abundance of CFTR. Here we identified the underlying biochemical mechanism using peptide pull-down assays followed by mass spectrometry. We identified in bronchial epithelial cells that the adaptor protein SHC1 recognizes tyrosine-phosphorylated CFTR through its phosphotyrosine-binding domain and that the formation of a complex between SHC1 and CFTR is induced at the PM in the presence of activated SYK. The depletion of endogenous SHC1 expression was sufficient to promote an increase in CFTR at the PM of these cells. The results identify a SYK/SHC1 pathway that regulates the PM levels of CFTR channels, contributing to a better understanding of how CFTR-mediated chloride secretion is regulated.

An Architecture for Reliable Transportation of Delicate Goods.

Adequate conditions are critical to avoiding damage or degradation of products during transportation, especially in the case of delicate goods like food products, live animals, precision machinery or art items, among others. The damages are not always readily identified: sometimes they are only detected several days or weeks after the merchandise has been delivered. Moreover, it may be hard to assess if the problems resulted from the transport conditions, and it may be even harder to prove it, making it difficult to determine and assign responsibilities. Also, transport is a global business, typically involving different companies and means (truck, train, plane, ship, …). Usually, customers hire the service to a single commercial entity, but the service is performed by several companies, like transporters, stockists and dispatchers. To know whether the transport requirements are fulfilled or not is thus essential to assessing responsibilities and encouraging compliance by all the players in the process. In this paper, the authors propose an architecture that allows certifying, in an exempt manner, the conditions under which the transport of sensitive goods are carried out. In case of compliance, it protects the entities of the transport chain and ensures the customer that the merchandise has not been subject to conditions that may have affected its integrity or quality. If problems are detected, it allows to identify the non-compliant players and to assign responsibilities. The solution is based on ultra-low-power, low-cost devices (equipped with several sensors, a real-time clock, and Bluetooth Low Energy services), a mobile application and several cloud services (including a Coordinated Universal Time service).

Inhibition of calpain 1 restores plasma membrane stability to pharmacologically rescued Phe508del-CFTR variant.

Cystic fibrosis (CF) is a genetic disease caused by mutations in the gene encoding CF transmembrane conductance regulator (CFTR), a chloride channel normally expressed at the surface of epithelial cells. The most frequent mutation, resulting in Phe-508 deletion, causes CFTR misfolding and its premature degradation. Low temperature or pharmacological correctors can partly rescue the Phe508del-CFTR processing defect and enhance trafficking of this channel variant to the plasma membrane (PM). Nevertheless, the rescued channels have an increased endocytosis rate, being quickly removed from the PM by the peripheral protein quality-control pathway. We previously reported that rescued Phe508del-CFTR (rPhe508del) can be retained at the cell surface by stimulating signaling pathways that coax the adaptor molecule ezrin (EZR) to tether rPhe508del-Na+/H+-exchange regulatory factor-1 complexes to the actin cytoskeleton, thereby averting the rapid internalization of this channel variant. However, the molecular basis for why rPhe508del fails to recruit active EZR to the PM remains elusive. Here, using a proteomics approach, we characterized and compared the core components of wt-CFTR- or rPhe508del-containing macromolecular complexes at the surface of human bronchial epithelial cells. We identified calpain 1 (CAPN1) as an exclusive rPhe508del interactor that prevents active EZR recruitment, impairs rPhe508del anchoring to actin, and reduces its stability in the PM. We show that either CAPN1 down-regulation or its chemical inhibition dramatically improves the functional rescue of Phe508del-CFTR in airway cells. These observations suggest that CAPN1 constitutes an appealing target for pharmacological intervention, as part of CF combination therapies restoring Phe508del-CFTR function.

WNK1 phosphorylation sites in TBC1D1 and TBC1D4 modulate cell surface expression of GLUT1.

Glucose uptake by mammalian cells is a key mechanism to maintain cell and tissue homeostasis and relies mostly on plasma membrane-localized glucose transporter proteins (GLUTs). Two main cellular mechanisms regulate GLUT proteins in the cell: first, expression of GLUT genes is under dynamic transcriptional control and is used by cancer cells to increase glucose availability. Second, GLUT proteins are regulated by membrane traffic from storage vesicles to the plasma membrane (PM). This latter process is triggered by signaling mechanisms and well-studied in the case of insulin-responsive cells, which activate protein kinase AKT to phosphorylate TBC1D4, a RAB-GTPase activating protein involved in membrane traffic regulation. Previously, we identified protein kinase WNK1 as another kinase able to phosphorylate TBC1D4 and regulate the surface expression of the constitutive glucose transporter GLUT1. Here we describe that downregulation of WNK1 through RNA interference in HEK293 cells led to a 2-fold decrease in PM GLUT1 expression, concomitant with a 60% decrease in glucose uptake. By mass spectrometry, we identified serine (S) 704 in TBC1D4 as a WNK1-regulated phosphorylation site, and also S565 in the paralogue TBC1D1. Transfection of the respective phosphomimetic or unphosphorylatable TBC1D mutants into cells revealed that both affected the cell surface abundance of GLUT1. The results reinforce a regulatory role for WNK1 in cell metabolism and have potential impact for the understanding of cancer cell metabolism and therapeutic options in type 2 diabetes.

Inflammatory Microenvironment Modulation of Alternative Splicing in Cancer: A Way to Adapt.

The relationship between inflammation and cancer has been long recognized by the medical and scientific community. In the last decades, it has returned to the forefront of clinical oncology since a wealth of knowledge has been gathered about the cells, cytokines and physiological processes that are central to both inflammation and cancer. It is now robustly established that chronic inflammation can induce certain cancers but also that solid tumors, in turn, can initiate and perpetuate local inflammatory processes that foster tumor growth and dissemination. Inflammation is the hallmark of the innate immune response to tissue damage or infection, but also mediates the activation, expansion and recruitment to the tissues of cells and antibodies of the adaptive immune system. The functional integration of both components of the immune response is crucial to identify and subdue tumor development, progression and dissemination. When this tight control goes awry, altered cells can avoid the immune surveillance and even subvert the innate immunity to promote their full oncogenic transformation. In this chapter, we make a general overview of the most recent data linking the inflammatory process to cancer. We start with the overall inflammatory cues and processes that influence the relationship between tumor and the microenvironment that surrounds it and follow the ever-increasing complexity of processes that end up producing subtle changes in the splicing of certain genes to ascertain survival advantage to cancer cells.

Alternative Splicing: Expanding the Landscape of Cancer Biomarkers and Therapeutics.

Alternative splicing (AS) is a critical post-transcriptional regulatory mechanism used by more than 95% of transcribed human genes and responsible for structural transcript variation and proteome diversity. In the past decade, genome-wide transcriptome sequencing has revealed that AS is tightly regulated in a tissue- and developmental stage-specific manner, and also frequently dysregulated in multiple human cancer types. It is currently recognized that splicing defects, including genetic alterations in the spliced gene, altered expression of both core components or regulators of the precursor messenger RNA (pre-mRNA) splicing machinery, or both, are major drivers of tumorigenesis. Hence, in this review we provide an overview of our current understanding of splicing alterations in cancer, and emphasize the need to further explore the cancer-specific splicing programs in order to obtain new insights in oncology. Furthermore, we also discuss the recent advances in the identification of dysregulated splicing signatures on a genome-wide scale and their potential use as biomarkers. Finally, we highlight the therapeutic opportunities arising from dysregulated splicing and summarize the current approaches to therapeutically target AS in cancer.

Tyrosine phosphorylation modulates cell surface expression of chloride cotransporters NKCC2 and KCC3.

Cellular chloride transport has a fundamental role in cell volume regulation and renal salt handling. Cellular chloride entry or exit are mediated at the plasma membrane by cotransporter proteins of the solute carrier 12 family. For example, NKCC2 resorbs chloride with sodium and potassium ions at the apical membrane of epithelial cells in the kidney, whereas KCC3 releases chloride with potassium ions at the basolateral membrane. Their ion transport activity is regulated by protein phosphorylation in response to signaling pathways. An additional regulatory mechanism concerns the amount of cotransporter molecules inserted into the plasma membrane. Here we describe that tyrosine phosphorylation of NKCC2 and KCC3 regulates their plasma membrane expression levels. We identified that spleen tyrosine kinase (SYK) phosphorylates a specific N-terminal tyrosine residue in each cotransporter. Experimental depletion of endogenous SYK or pharmacological inhibition of its kinase activity increased the abundance of NKCC2 at the plasma membrane of human embryonic kidney cells. In contrast, overexpression of a constitutively active SYK mutant decreased NKCC2 membrane abundance. Intriguingly, the same experimental approaches revealed the opposite effect on KCC3 abundance at the plasma membrane, compatible with the known antagonistic roles of NKCC and KCC cotransporters in cell volume regulation. Thus, we identified a novel pathway modulating the cell surface expression of NKCC2 and KCC3 and show that this same pathway has opposite functional outcomes for these two cotransporters. The findings have several biomedical implications considering the role of these cotransporters in regulating blood pressure and cell volume.

Novel applications of waste foundry sand in conventional and dry-mix concretes.

The use of waste materials in the building industry is a major challenge for eco-efficient construction. Brazil generates more than 3 million tons of waste foundry sand (WFS) annually, making it one of the largest industrial wastes produced in the country. This work proposes the use of WFS in two novel ways: in conventional concrete by WFS calcination, and in dry-mix concrete for the production of concrete blocks. For the conventional mixture study, mortars with 0, 50 and 100% replacement of natural sand by WFS and calcined WFS (CFS) were produced. The fresh state properties, volumetric variation, cement hydration and 28-days compressive strength of the mortars were evaluated. For the dry-mix concrete study, compositions with two densities (2.20 and 2.25 g/cm3), three cement contents and 0, 50 and 100% WFS in natural sand replacement were produced in the laboratory. Furthermore, concrete blocks of different strength ranges and 0 and 100% WFS in natural sand replacement were produced in a concrete block manufacturing plant for full-scale testing. The results showed that the use of WFS led to reductions in flowability and compressive strength of the mortars, but did not cause expansion as initially expected. In contrast, the use of up to 100% CFS resulted in mortars with flowability and compressive strength similar to those of the reference. WFS calcination removed the pulverized coal and may have formed pozzolanic phases in the clay material. As a result, the CFS presented performance similar to that of natural sand. In dry-mix concrete, the laboratory results showed that the use of 100% WFS resulted in similar strengths to the reference for concretes of up to 20 MPa. Finally, full-scale tests showed that it was possible to produce concrete blocks with 100% WFS and strengths compatible to the reference.

Targeting Colon Cancers with Mutated BRAF and Microsatellite Instability.

The subgroup of colon cancer (CRC) characterized by mutation in the BRAF gene and high mutation rate in the genomic DNA sequence, known as the microsatellite instability (MSI) phenotype, accounts for roughly 10% of the patients and derives from polyps with a serrated morphology. In this review, both features are discussed with regard to therapeutic opportunities. The most prevalent cancer-associated BRAF mutation is BRAF V600E that causes constitutive activation of the pro-proliferative MAPK pathway. Unfortunately, the available BRAF-specific inhibitors had little clinical benefit for metastatic CRC patients due to adaptive MAPK reactivation. Recent contributions for the development of new combination therapy approaches to pathway inhibition will be highlighted. In addition, we review the promising role of the recently developed immune checkpoint therapy for the treatment of this CRC subtype. The MSI phenotype of this subgroup results from an inactivated DNA mismatch repair system and leads to frameshift mutations with translation of new amino acid stretches and the generation of neo-antigens. This most likely explains the observed high degree of infiltration by tumour-associated lymphocytes. As cytotoxic lymphocytes are already part of the tumour environment, their activation by immune checkpoint therapy approaches is highly promising.

Targeting the serrated pathway of colorectal cancer with mutation in BRAF.

A recently acknowledged morphological pathway to colorectal cancer originates from precursor polyps with a serrated appearance due to branching and folding of the colon epithelium. This serrated origin accounts for up to 30% of all colorectal tumors but these are heterogeneous regarding molecular characteristics and patient outcome. Here we review the current knowledge about the classification of this tumor subtype and its association with five key features: mutation status of the BRAF or KRAS genes, the CpG island methylation phenotype, microsatellite instability, immune cell infiltration, and overexpression of GTPase RAC1b. Subsequently, available therapeutic approaches for targeting these molecular characteristics are presented and critically discussed.

The third dimension: new developments in cell culture models for colorectal research.

Cellular models are important tools in various research areas related to colorectal biology and associated diseases. Herein, we review the most widely used cell lines and the different techniques to grow them, either as cell monolayer, polarized two-dimensional epithelia on membrane filters, or as three-dimensional spheres in scaffold-free or matrix-supported culture conditions. Moreover, recent developments, such as gut-on-chip devices or the ex vivo growth of biopsy-derived organoids, are also discussed. We provide an overview on the potential applications but also on the limitations for each of these techniques, while evaluating their contribution to provide more reliable cellular models for research, diagnostic testing, or pharmacological validation related to colon physiology and pathophysiology.

Trypanosoma cruzi infection in captive Neotropical primates in the Brazilian Amazon.

The aim of this study was to detect the infection by Trypanosoma cruzi in captive Neotropical primates in the Brazilian Amazon. From February 2013 to July 2014, 112 blood samples were collected from Neotropical primates from the Amazonas, Amapá, and Pará States, north of Brazil. The subjects belonged to the families Cebidae (N = 59), Atelidae (N = 41), Callitrichidae (N = 5), Pitheciidae (N = 4), and Aotidae (N = 3). Blood smears also were examined for the presence of trypomastigotes by optical microscopy. For the detection of T. cruzi DNA, a Nested-PCR with primers TCZ1/TCZ2 and TCZ3/TCZ4 was performed. T. cruzi DNA was detected in 12.5% (14/112) of Neotropical primates examined. Positive samples were detected in 16%, 12.5%, and 11.11% of the different species of primates sampled from the Amapá, Pará, and Amazonas states, respectively. The analysis of the blood smears did not reveal trypomastigote forms of T. cruzi. In conclusion, Neotropical primates kept in captivity were infected by T. cruzi in the studied areas. We recommend that a health management protocol be put into place to prevent the transmission of infectious agents among captive populations, captive and wild populations, and between NHPs and the technicians who handle these animals.

Phosphorylation of SRSF1 by SRPK1 regulates alternative splicing of tumor-related Rac1b in colorectal cells.

The premessenger RNA of the majority of human genes can generate various transcripts through alternative splicing, and different tissues or disease states show specific patterns of splicing variants. These patterns depend on the relative concentrations of the splicing factors present in the cell nucleus, either as a consequence of their expression levels or of post-translational modifications, such as protein phosphorylation, which are determined by signal transduction pathways. Here, we analyzed the contribution of protein kinases to the regulation of alternative splicing variant Rac1b that is overexpressed in certain tumor types. In colorectal cells, we found that depletion of AKT2, AKT3, GSK3ß, and SRPK1 significantly decreased endogenous Rac1b levels. Although knockdown of AKT2 and AKT3 affected only Rac1b protein levels suggesting a post-splicing effect, the depletion of GSK3ß or SRPK1 decreased Rac1b alternative splicing, an effect mediated through changes in splicing factor SRSF1. In particular, the knockdown of SRPK1 or inhibition of its catalytic activity reduced phosphorylation and subsequent translocation of SRSF1 to the nucleus, limiting its availability to promote the inclusion of alternative exon 3b into the Rac1 pre-mRNA. Altogether, the data identify SRSF1 as a prime regulator of Rac1b expression in colorectal cells and provide further mechanistic insight into how the regulation of alternative splicing events by protein kinases can contribute to sustain tumor cell survival.