The Yin and Yang of cancer genes

Bashyam, Murali D.; Animireddy, Srinivas; Bala, Pratyusha; Naz, Ashmala; George, Sara Anisa

doi:10.1016/j.gene.2019.04.025

Cited by 24 publications

(18 citation statements)

References 151 publications

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“…In conclusion, ARID1B appears to contribute to oncogenesis through non-canonical cytoplasm-based mechanisms in addition to mechanisms involving dysregulation in the nucleus (figure S7), adding to the growing list of cancer genes exhibiting a dual ‘Yin-Yang’ nature 2 . The results presented here have potentially opened an exciting new area of ARID1B and SWI/SNF biology.…”

Section: Discussionmentioning

confidence: 95%

Cytoplasm localized ARID1B promotes oncogenesis in pancreatic cancer by activating RAF-ERK signaling

Animireddy

Kavadipula

Kotapalli

et al. 2019

Preprint

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The ARID1B/BAF250b subunit of the human SWI/SNF chromatin remodeling complex is a canonical nuclear tumor suppressor. Immunohistochemistry on a pancreatic cancer tissue microarray revealed significant ARID1B cytoplasmic localization that correlated with advanced tumor stage and lymph node positivity. Identification of the nuclear localization signal (NLS) using in silico prediction and subcellular localization studies facilitated evaluation of a possible cytoplasmic function for ARID1B. A cytoplasm-restricted ARID1B-NLS mutant was significantly compromised to regulate transcription activation and tumor suppression functions, as expected. Surprisingly however, cytoplasm-localized ARID1B could bind c-RAF and PPP1CA causing stimulation of RAS-RAF-ERK signaling and β-catenin transcription activity in pancreatic cancer cells. More importantly, cytoplasmic ARID1B resulted in an induction of cell growth and migration in pancreatic cancer cell lines that was dependent on ERK signaling and caused increased tumorigenesis in nude mice. NLS peptides representing mutations identified from pancreatic cancer samples exhibiting ARID1B cytoplasmic localization or curated from cancer somatic mutation database were significantly compromised to effect nuclear localization of a reporter protein. ARID1B cytoplasmic localization correlated significantly with active forms of ERK and β-catenin in primary pancreatic tumor samples. ARID1B may therefore promote oncogenesis through non-canonical cytoplasm-based gain of function mechanisms in addition to dysregulation in the nucleus.

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Section: Discussionmentioning

confidence: 95%

Cytoplasm localized ARID1B promotes oncogenesis in pancreatic cancer by activating RAF-ERK signaling

Animireddy

Kavadipula

Kotapalli

et al. 2019

Preprint

Self Cite

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“…Tumour development is a process stretched over time (most commonly it lasts 5-20 years), and its multi-stage course is determined by mutations which accumulate in the cell, leading to a change in its biological properties [14]. In 2011, Hanahan • "escape" from the immune system's "supervision" mechanism.…”

Section: Genetic Basis Of Cancermentioning

confidence: 99%

“…Suppressor genes are classified as "gatekeepers" because they control cell division points, directing mutated cells to a path of repair of DNA damage or to programmed death (apoptosis). Finally, mutator genes are referred to as "caretakers" and they are responsible for removing unpaired and mispaired bases from DNA, as such bases are the cause of mutation [14].…”

Section: Genetic Basis Of Cancermentioning

confidence: 99%

“…Cancer development, clinical course and response to therapy are affected by these three groups of genes of key impact on neoplastic transformation (genes of high penetrance), but also by many genes of moderate and low penetrance (e.g. genes which are involved in the process of angiogenesis, cell array adhesion, affect the organism's immune reaction, localised tumour development, metastasis potential, reaction to therapy and many other processes) [14].…”

Section: Genetic Basis Of Cancermentioning

confidence: 99%

“…Instability may be expressed on the chromosome level (aberrations of the number and structure of chromosomes), gene level (accumulation of mutations) or in alterations of epigenetic regulation of gene expression (global hypomethylation which contributes to cells' chromosomal instability and hypermethylation of suppressor and mutator genes, thus leading to loss of their function). Accumulation of genetic alterations in cells causes changes of their biological properties and also leads to development of resistance to the therapy [14,19].…”

Section: Genetic Basis Of Cancermentioning

confidence: 99%

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Fundamentals of personalised medicine in genetic testing-based oncology

Sąsiadek

Łaczmańska

Maciejczyk

et al. 2020

Nowotwory. Journal of Oncology

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The dynamic development of genetics in recent decades has opened a new era in medicine. Understanding molecular mechanisms of multiple human diseases has laid the foundations for targeted medical care, based on knowledge of the basic pathogenesis of these diseases. This breakthrough is particularly evident in oncology because knowledge of the molecular basis of cancer leads to a change in the paradigm of medical care for the patients. Gradually, classification and treatment based only on organ location and histopathologic diagnosis is becoming outdated, and so is the classification considering clinical stage and malignancy of the tumour. Personalized treatment for individual patients based on the profile of genetic changes is increasingly common. Defining the genetic aetiology of neoplastic diseases was an achievement that allowed for division of neoplasms into sporadic ones and those which develop due to hereditary predisposition. It also enabled establishment of the molecular classification of neoplasms and more and more frequently-targeted treatment and precise clinical prognosis. This article is the first one in a series of articles written by oncologists and geneticists. We hope that this series will be helpful for oncologists in understanding genetic problems and for geneticists-in understanding oncologic issues.

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2023

Concepts in Biology

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The Yin and Yang of cancer genes

Cited by 24 publications

References 151 publications

Cytoplasm localized ARID1B promotes oncogenesis in pancreatic cancer by activating RAF-ERK signaling

Cytoplasm localized ARID1B promotes oncogenesis in pancreatic cancer by activating RAF-ERK signaling

Fundamentals of personalised medicine in genetic testing-based oncology

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