Publications by authors named "Anwesha B Ghosh"

4 Publications

  • Page 1 of 1

Chromosome 3q26 Gain Is an Early Event Driving Coordinated Overexpression of the PRKCI, SOX2, and ECT2 Oncogenes in Lung Squamous Cell Carcinoma.

Cell Rep 2020 01;30(3):771-782.e6

Department of Cancer Biology, Mayo Clinic Florida, Jacksonville, FL 32224, USA. Electronic address:

Lung squamous cell carcinoma (LSCC) is a prevalent form of lung cancer exhibiting distinctive histological and genetic characteristics. Chromosome 3q26 copy number gain (CNG) is a genetic hallmark of LSCC present in >90% of tumors. We report that 3q26 CNGs occur early in LSCC tumorigenesis, persist during tumor progression, and drive coordinate overexpression of PRKCI, SOX2, and ECT2. Overexpression of PRKCI, SOX2, and ECT2 in the context of Trp53 loss is sufficient to transform mouse lung basal stem cells into tumors with histological and genomic features of LSCC. Functionally, PRKCI and SOX2 collaborate to activate an extensive transcriptional program that enforces a lineage-restricted LSCC phenotype, whereas PRKCI and ECT2 collaborate to promote oncogenic growth. Gene signatures indicative of PKCĪ¹-SOX2 and PKCĪ¹-ECT2 signaling activity are enriched in the classical subtype of human LSCC and predict distinct therapeutic vulnerabilities. Thus, the PRKCI, SOX2, and ECT2 oncogenes represent a multigenic driver of LSCC.
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http://dx.doi.org/10.1016/j.celrep.2019.12.071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238436PMC
January 2020

Hid arbitrates collective cell death in the Drosophila wing.

Mech Dev 2015 Nov 29;138 Pt 3:349-55. Epub 2015 Jul 29.

Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390-9039, United States. Electronic address:

Elimination of cells and tissues by apoptosis is a highly conserved and tightly regulated process. In Drosophila, the entire wing epithelium is completely removed shortly after eclosion. The cells that make up this epithelium are collectively eliminated through a highly synchronized form of apoptotic cell death, involving canonical apoptosome genes. Here we present evidence that collective cell death does not require cell-cell contact and show that transcription of the IAP antagonist, head involution defective, is acutely induced in wing epithelial cells prior to this process. hid mRNAs accumulate to levels that exceed a component of the ribosome and likewise, Hid protein becomes highly abundant in these same cells. hid function is required for collective cell death, since loss of function mutants shows persisting wing epithelial cells and, furthermore, silencing of the hormone bursicon in the CNS produced collective cell death defective phenotypes manifested in the wing epithelium. Taken together, our observations suggest that acute induction of Hid primes wing epithelial cells for collective cell death and that Bursicon is a strong candidate to trigger this process, possibly by activating the abundant pool of Hid protein already present.
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http://dx.doi.org/10.1016/j.mod.2015.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679717PMC
November 2015

G protein-coupled receptors and the regulation of autophagy.

Trends Endocrinol Metab 2014 May 18;25(5):274-82. Epub 2014 Apr 18.

Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9041, USA. Electronic address:

Autophagy is an important catabolic cellular process that eliminates damaged and unnecessary cytoplasmic proteins and organelles. Basal autophagy occurs during normal physiological conditions, but the activity of this process can be significantly altered in human diseases. Thus, defining the regulatory inputs and signals that control autophagy is essential. Nutrients are key modulators of autophagy. Although autophagy is generally accepted to be regulated in a cell-autonomous fashion, recent studies suggest that nutrients can modulate autophagy in a systemic manner by inducing the secretion of hormones and neurotransmitters that regulate G protein-coupled receptors (GPCRs). Emerging studies show that GPCRs also regulate autophagy by directly detecting extracellular nutrients. We review the role of GPCRs in autophagy regulation, highlighting their potential as therapeutic drug targets.
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http://dx.doi.org/10.1016/j.tem.2014.03.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082244PMC
May 2014

The G protein-coupled taste receptor T1R1/T1R3 regulates mTORC1 and autophagy.

Mol Cell 2012 Sep 6;47(6):851-62. Epub 2012 Sep 6.

Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Dallas, TX 75390-9041, USA.

Cells continually assess their energy and nutrient state to maintain growth and survival and engage necessary homeostatic mechanisms. Cell-autonomous responses to the fed state require the surveillance of the availability of amino acids and other nutrients. The mammalian target of rapamycin complex 1 (mTORC1) integrates information on nutrient and amino acid availability to support protein synthesis and cell growth. We identify the G protein-coupled receptor (GPCR) T1R1/T1R3 as a direct sensor of the fed state and amino acid availability. Knocking down this receptor, which is found in most tissues, reduces the ability of amino acids to signal to mTORC1. Interfering with this receptor alters localization of mTORC1, downregulates expression of pathway inhibitors, upregulates key amino acid transporters, blocks translation initiation, and induces autophagy. These findings reveal a mechanism for communicating amino acid availability through a GPCR to mTORC1 in mammals.
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http://dx.doi.org/10.1016/j.molcel.2012.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749915PMC
September 2012
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