No abstract

In the past 3 years, altered expression of the HEF1/CAS-L/ NEDD9 scaffolding protein has emerged as contributing to cancer metastasis in multiple cancer types. However, whereas some studies have identified elevated NEDD9 expression as prometastatic, other work has suggested a negative role in tumor progression. We here show that the Nedd9-null genetic background significantly limits mammary tumor initiation in the MMTV-polyoma virus middle T genetic model. Action of NEDD9 is tumor cell intrinsic, with immune cell infiltration, stroma, and angiogenesis unaffected. The majority of the late-appearing mammary tumors of MMTV-polyoma virus middle T;Nedd9 À/À mice are characterized by depressed activation of proteins including AKT, Src, FAK, and extracellular signal-regulated kinase, emphasizing an important role of NEDD9 as a scaffolding protein for these prooncogenic proteins. Analysis of cells derived from primary Nedd9 +/+ and Nedd9 À/À tumors showed persistently reduced FAK activation, attachment, and migration, consistent with a role for NEDD9 activation of FAK in promoting tumor aggressiveness. This study provides the first in vivo evidence of a role for NEDD9 in breast cancer progression and suggests that NEDD9 expression may provide a biomarker for tumor aggressiveness.

Upregulation of the scaffolding protein HEF1, also known as NEDD9 and Cas-L, has recently been identified as a pro-metastatic stimulus in a number of different solid tumors, and has also been strongly associated with pathogenesis of BCR-Abl-dependent tumors. As the evidence mounts for HEF1/NEDD9/Cas-L as a key player in metastatic cancer, it is timely to review the molecular regulation of HEF1/NEDD9/Cas-L. Most of the mortality associated with cancer arises from uncontrolled metastases, thus a better understanding of the properties of proteins specifically associated with promotion of this process may yield insights that improve cancer diagnosis and treatment. In this review, we summarize the extensive literature regarding HEF1/NEDD9/Cas-L expression and function in signaling relevant to cell attachment, migration, invasion, cell cycle, apoptosis, and oncogenic signal transduction. The complex function of HEF1/NEDD9/Cas-L revealed by this analysis leads us to propose a model in which alleviation of cell cycle checkpoints and acquired resistance to apoptosis is permissive for a HEF1/NEDD9/Cas-L-promoted pro-metastatic phenotype.

Purpose: In 2020, in response to the emergence and global spread of the disease COVID-19, caused by a new variant of coronavirus 2019-nCoV, the government of India ordered a nationwide lockdown for 21 days, which was then extended to a total of over 50 days. The aim of this study is to assess the effect of the lockdown on ophthalmic training programs across India. Methods: An online survey was sent across to trainee ophthalmologists across India through various social media platforms. Results: In all, 716 trainees responded; the average age was 29.1 years. Results showed that majority of the respondents were enrolled in residency programs (95.6%; 685/716) and the others were in fellowship programs. About 24.6% (176/716) of the trainees had been deployed on 'COVID-19 screening' duties. Nearly 80.7% (578/716) of the trainees felt that the COVID-19 lockdown had negatively impacted their surgical training. Furthermore, 54.8% (392/716) of the trainees perceived an increase in stress levels during the COVID-19 lockdown and 77.4% (554/716) reported that their family members had expressed an increased concern for their safety and wellbeing since the lockdown began. In all, 75.7% (542/716) of the respondents felt that online classes and webinars were useful during the lockdown period. Conclusion: Our survey showed that majority ophthalmology trainees across the country felt that the COVID-19 lockdown adversely affected their learning, especially surgical training. While most found online classes and webinars useful, the trainees' perceived stress levels were higher than normal during the lockdown. Training hospitals should take cognizance of this and reassure trainees; formulate guidelines to augment training to compensate for the lost time as well as mitigate the stress levels upon resumption of regular hospital services and training. Going ahead, permanent changes such as virtual classrooms and simulation-based training should be considered.