The roles of vasohibin and its family members: Beyond angiogenesis modulators

Abstract

Vasohibin-1 is an intrinsic angiogenesis inhibitor, and is expressed in endothelial cells via induction by pro-angiogenesis factors. It is known to inhibit several processes of angiogenesis, with different mechanisms from extrinsic angiogenesis inhibitors. Vasohibin-2 is mainly expressed by mononuclear cells which have been mobilized from bone marrow. It not only promotes angiogenesis, but also modulates the releases of FGF-2 and VEGF, which are the two major inducers for vasohibin1. Hypoxic environment induces the expression of hypoxia-inducible Factor 1α with a result of VEGF release nearly in all tumor cell lines and tissues. However, it has been observed that hypoxia reduces the inducible effects of VEGF on vasohibin, which indicates that a complicated mechanism exists in the angiogenesis. Vasohibin and its family members play important roles in both the physiological and pathological procedures, in contrary but complementary patterns. Furthermore, human aortic smooth muscle cells and fibroblast have also been detected to express vasohibin on a moderate to weak scale range. Recently, the results of an increasing number of studies in vivo have shown that vasohibin can also be detected in several cancers, and is associated with micro-vessel densities, histology grades, invasions, poor clinical features, metastasis, and dissemination in abdominal cavities, as well as EMT. In more recent reports, it has been confirmed that, along with being angiogenesis regulators, a variety of other roles have been associated with this family. The focus of this study was the upstream regulatory mechanisms of vasohibin expressions, and their role in regard to the downstream target proteins of vasohibin, especially in carcinoma. Vasohibin is considered to be an original angiogenesis inhibitor, and has a much broader significance in pathological processes. It can be taken as an independent prognostic factor, as well as a potential strategy for cancer therapy programs.

The safety and efficacy of TACE combined with apatinib on patients with advanced hepatocellular carcinoma: a retrospective study

“…Angiogenesis facilitate the supply of oxygen and nutrients to tumor cells, and therefore plays a critical role in tumor growth, development and metastasis. 8 Tyrosine kinase inhibitors (TKIs) such as sorafenib and regorafenib suppress vessel growth, and they have been shown to exert some survival benefit for HCC patients. 9,10 Therefore, to evaluate the antineoplastic effect of anti-angiogenic therapy is critical in HCC treatment.…”

Intrinsic and Extrinsic Factors Affecting Microtubule Dynamics in Normal and Cancer Cells

“…Downregulation of TTL and increased α-tubulin detyrosination were reported during the epithelial-mesenchymal transition (EMT) that occurs during tumor invasion [245] in prostate cancer cells [246], in aggressive subtypes of breast cancer cells [247], and in primary neuroblastomas with poor prognosis [248]. The recent discovery of the vasohibin (VASH)/small vasohibin-binding protein (SVBP) complex, reported as a detyrosinating enzyme, tubulin carboxypeptidase (TCP) [249,250], provides new links between this tubulin modification and already known associations between vasohibin dysfunction and cancer [251,252].…”

The emerging role of tubulin posttranslational modifications in cilia and ciliopathies

“…Male infertility in glutamylation/ deglutamylation enzymes mutated mice (Campbell et al 2002, Giordano et al 2019, Konno et al 2016, Mullen et al 1976, Vogel et al 2010 Respiratory disorders in TTLL1 mutated mice (Ikegami et al 2010) Retinal degenerative diseases in mice and human with abnormal glutamylation (Grau et al 2017, Marchena et al 2011 Decreased axonemal polyglutamylation in Joubert syndrome patients with certain gene mutation ( Regulate the stability and maintenance of motile cilia Bosch (Grau et al 2013, Pathak et al 2011 Modulate the length of primary cilium (Gadadhar et al 2017b) Reciprocal or competition of glutamylation (Gadadhar et al 2017b Retinal degeneration in TTLL3 -/mice (Grau et al 2017) Suppression of TTLL3 in colon carcinogenesis (Rocha et al 2014) Detyrosination (Erck et al 2005) Muscle and cardiac dysfunctions (Kerr et al 2015, Robison et al 2016 Development of several types of cancer (Kato et al 2004, Mialhe et al 2001, Du et al 2017 Although the aK40 acetylation of tubulin has been discovered over 30 years, its biological importance in cilia only emerges recently. Cells lacking of aTAT1 lost acetylation but preserve unaffected cilia morphology (Kalebic et al 2013b;Shida et al 2010).…”