Nav: Home

Oncotarget: hPCL3S promotes proliferation and migration of androgen-independent prostate cancer cells

March 25, 2020

The cover for issue 12 of Oncotarget features Figure 11, "Global analyses of the RNA-Seq data of LNCaP empty vector and LNCaP cells overexpressing hPCL3S (Clone 12)" by Abdelfettah, et al.

These proteins contain a TUDOR domain binding H3K36me3, two PHD domains and a Winged-helix domain involved in GC-rich DNA binding.

The human PCL3 locus encodes the full-length hPCL3L protein and a shorter isoform, hPCL3S containing the TUDOR and PHD1 domains only.

A mutant hPCL3S unable to bind H3K36me3 increased proliferation and migration of LNCa P similarly to wt hPCL3S whereas inactivation of its PHD1 domain decreased proliferation.

Dr. Dominique Leprince from the University de Lille, CNRS, Institut Pasteur de Lille, UMR 8161m M3T, Mechanisms of Tumorigenesis and Targeted Therapies, F-59000 Lille, France said, "Prostate cancer (PCa) is the second most common type of cancer diagnosed worldwide and is still a leading cause of death despite recent research advances."

"Prostate cancer (PCa) is the second most common type of cancer diagnosed worldwide and is still a leading cause of death despite recent research advances"

- Dr. Dominique Leprince, University de Lille, CNRS, Institut Pasteur de Lille, UMR 8161m M3T, Mechanisms of Tumorigenesis and Targeted Therapies
Two of most commonly used prostate cancer cell lines LNCa P and PC3 are representative of prostatic adenocarcinoma and of Small Cell Neuroendocrine Carcinomas, respectively.

These proteins share a structured N-terminal domain consisting of a TUDOR domain, two PHD domains followed by a Winged-helix domain involved in GC-rich DNA binding and a C-terminal reverse Chromodomain.

Indeed, PHF1 through its PHD1 domain is the only human Polycomb-like protein capable of inducing cell quiescence by interacting with P53 to stabilize it independently of its TUDOR domain and thus of its binding at chromatin.

In this study, the authors have quantified the expression levels of both hPCL3 isoforms in primary prostate tumors as well as in the hormone-dependent LNCa P and hormone-independent DU145 and PC3 prostate cancer cell lines.

Collectively, their results provide insights into a new mechanism whereby AR-independent prostate cancer cell lines acquire heightened ability to proliferate and migrate and highlight hPCL3S targeting as a new potential interventional strategy against castration resistant prostate cancers.

The Leprince Research Team concluded in their Oncotarget Research Paper, "we demonstrated that overexpression of hPCL3S promoted proliferation, anchorage-independent growth and migration in human LNCaP prostate cancer cells whereas silencing of endogenous hPCL3S in DU145 and PC3 prostate cancer cells impaired these effects. Furthermore, our results suggested that hPCL3S did not act through the perturbation of PRC2 activity but rather mainly through chromatin-independent effects relying on its PHD1 domain. Therefore, our studies could have identified the overexpression of hPCL3S as a new alteration contributing to tumor progression in prostate cancer through the emergence of a rapidly growing cell population of neuroendocrine-like cells."
-end-
Sign up for free Altmetric alerts about this article

DOI - https://doi.org/10.18632/oncotarget.27511

Full text - https://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=27511&path%5B%5D=90171

Correspondence to - Dominique Leprince - dominique.leprince@ibl.cnrs.fr

Keywords - hPCL3S, PHF19, PRC2, β-catenin, prostate cancer

About Oncotarget

Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:

SoundCloud -https://soundcloud.com/oncotarget
Facebook -https://www.facebook.com/Oncotarget/
Twitter -https://twitter.com/oncotarget
LinkedIn -https://www.linkedin.com/company/oncotarget
Pinterest -https://www.pinterest.com/oncotarget/
Reddit -https://www.reddit.com/user/Oncotarget/

Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls

Media Contact
MEDIA@IMPACTJOURNALS.COM
18009220957x105

Impact Journals LLC

Related Prostate Cancer Articles:

Major trial shows breast cancer drug can hit prostate cancer Achilles heel
A drug already licensed for the treatment of breast and ovarian cancers is more effective than targeted hormone therapy at keeping cancer in check in some men with advanced prostate cancer, a major clinical trial reports.
The Lancet: Prostate cancer study finds molecular imaging could transform management of patients with aggressive cancer
Results from a randomised controlled trial involving 300 prostate cancer patients find that a molecular imaging technique is more accurate than conventional medical imaging and recommends the scans be introduced into routine clinical practice.
Common genetic defect in prostate cancer inspires path to new anti-cancer drugs
Researchers found that, in prostate cancer, a mutation leading to the loss of one allele of a tumor suppressor gene known as PPP2R2A is enough to worsen a tumor caused by other mutations.
First prostate cancer therapy to target genes delays cancer progression
For the first time, prostate cancer has been treated based on the genetic makeup of the cancer, resulting in delayed disease progression, delayed time to pain progression, and potentially extending lives in patients with advanced, metastatic prostate cancer, reports a large phase 3 trial.
Men taking medications for enlarged prostate face delays in prostate cancer diagnosis
University of California San Diego School of Medicine researchers report that men treated with medications for benign prostatic hyperplasia (enlarged prostate) experienced a two-year delay in diagnosis of their prostate cancer and were twice as likely to have advanced disease upon diagnosis.
CNIO researchers confirm links between aggressive prostate cancer and hereditary breast cancer
The study has potential implications for families with members suffering from these types of tumours who are at an increased risk of developing cancer.
Distinguishing fatal prostate cancer from 'manageable' cancer now possible
Scientists at the University of York have found a way of distinguishing between fatal prostate cancer and manageable cancer, which could reduce unnecessary surgeries and radiotherapy.
Researchers find prostate cancer drug byproduct can fuel cancer cells
A genetic anomaly in certain men with prostate cancer may impact their response to common drugs used to treat the disease, according to new research at Cleveland Clinic.
ASCO and Cancer Care Ontario update guideline on radiation therapy for prostate cancer
The American Society of Clinical Oncology (ASCO) and Cancer Care Ontario today issued a joint clinical practice guideline update on brachytherapy (internal radiation) for patients with prostate cancer.
Patient prostate tissue used to create unique model of prostate cancer biology
For the first time, researchers have been able to grow, in a lab, both normal and primary cancerous prostate cells from a patient, and then implant a million of the cancer cells into a mouse to track how the tumor progresses.
More Prostate Cancer News and Prostate Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Meditations on Loneliness
Original broadcast date: April 24, 2020. We're a social species now living in isolation. But loneliness was a problem well before this era of social distancing. This hour, TED speakers explore how we can live and make peace with loneliness. Guests on the show include author and illustrator Jonny Sun, psychologist Susan Pinker, architect Grace Kim, and writer Suleika Jaouad.
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.