Baldwin AT et al. (2016) J Cell Sci "Unique and redundant -catenin regulatory roles of two Dishevelled paralogs during C. elegans asymmetric cell division."

Phillips BT, Clemons AM, Baldwin AT

[J Cell Sci, 2016]

The Wnt/-catenin signaling pathway is utilized across metazoans. However, the mechanism of signal transduction, especially dissociation of the -catenin destruction complex by Dishevelled proteins, remains controversial. Here we describe the function of the Dishevelled paralogs DSH-2 and MIG-5 in the Wnt/-catenin Asymmetry (WA) pathway in Caenorhabditis elegans, where WA drives asymmetric cell divisions throughout development. We find that DSH-2 and MIG-5 redundantly regulate cell fate in hypodermal seam cells. Similarly, both DSH-2 and MIG-5 are required for negative regulation of SYS-1/-catenin localization, but MIG-5 has a stronger effect on polarity of SYS-1 localization. We show that MIG-5 controls cortical APR-1/APC localization. DSH-2 and MIG-5 both regulate the localization of WRM-1/-catenin, acting together as negative regulators of WRM-1 nuclear localization. Finally, we demonstrate that overexpression of DSH-2 or MIG-5 in seam cells leads to stabilization of SYS-1 in the anterior seam daughter, solidifying the Dishevelleds as positive regulators of SYS-1/-catenin. Overall, we have further defined the role of Dishevelled in the WA signaling pathway, and demonstrated that DSH-2 and MIG-5 regulate cell fate, -catenin nuclear levels and polarity of -catenin regulation.

Akhoon BA et al. (2018) Exp Gerontol "Withanolide A extends the lifespan in human EGFR-driven cancerous Caenorhabditis elegans."

Rathor L, Pandey R, Akhoon BA

[Exp Gerontol, 2018]

The conserved EGFR pathway is linked with multiple cancers in humans including breast, ovarian, and lung carcinoma. Withanolide A, one of the major withanolidal active compounds isolated from the Withania somnifera, extends lifespan and ameliorates stress resistance in wild-type C. elegans by targeting the Insulin/IGF-1 signaling pathway. Up-regulation of IGF1 can transactivate EGFR which inturn reduces longevity and promotes tumor development in an organism. We examined the effects of Withanolide A on the lifespan of a human EGFR-driven C. elegans transgenic model exhibiting the multivulva (Muv) phenotype. The results showed that WA extends the lifespan of both wild human EGFR-driven C. elegans model (human wild-type tyrosine kinase) as well as models bearing single (L858R), and double mutations (T790M-L858R). The lifespan extension observed in these transgenic strains was 20.35, 24.21 and 21.27%, respectively. Moreover, the reduced fat levels were noticed in both wild-type N2 worms and transgenic strains. These observations support the heathspan promoting effect of WA as lipid-rich diet has been reported to promote tumor development. In view of the fact that most of the well known FDA approved drugs such as gefitinib fail to inhibit the EGFR-associated cancers because of these mutations, the present findings show the potential of Withanolide A as a foreseen future nutraceutical to improve the average survival of cancer patients.

Higazi TB et al. (2011) Am J Trop Med Hyg "Polymerase chain reaction pool screening used to compare prevalence of infective black flies in two onchocerciasis foci in northern Sudan."

Hassan HK, Richards F, Mackenzie CD, Mohamed HA, Higazi TB, Unnasch TR, Deran TC, Aziz N, ElMubark WA, Mohamed WA, Zarroug IM, Katabarwa M

[Am J Trop Med Hyg, 2011]

Onchocerciasis remains an important debilitating disease in many areas of Africa, including Sudan. The status of infection transmission in 2007 was assessed in the vectors of two disease foci in Sudan: Abu Hamed in northern Sudan, which has received at least 10 years of annual treatment and Galabat focus in eastern Sudan, where only minor, largely undocumented treatment activity has occurred. Assessment of more than 30,000 black flies for Onchocerca volvulus infectious stage L3 larvae by using an O-150 polymerase chain reaction protocol showed that black fly infectivity rates were 0.84 (95% confidence interval = 0.0497-1.88) per 10,000 flies for Abu Hamed and 6.9 (95% confidence interval = 1.1-16.4) infective flies per 10,000 for Galabat. These results provide entomologic evidence for suppressed Onchocerca volvulus transmission in the Abu Hamed focus and a moderate transmission rate of the parasite in the Galabat focus.