BECN1-knockout impairs tumor growth, migration and invasion by suppressing the cell cycle and partially suppressing the epithelial-mesenchymal transition of human triple-negative breast cancer cells

International Journal of Oncology
Cheng-Lin WuPing-Kun Zhou

Abstract

Beclin1 (BECN1), which directly interacts with B‑cell lymphoma 2, serves an important role in autophagy and is involved in the tumorigenesis of various types of cancer. However, the definite role of BECN1 in breast cancer remains controversial. Bi-allelic knockout of Becn1 in a mouse model leads to an embryonic lethal phenotype, which hampers further investigation. To generate cell lines with knockout of BECN1, the CRISPR/Cas9 technique was used to disrupt BECN1 in human triple-negative breast cancer (TNBC) MDA‑MB‑231 cells. To the best of our knowledge, the present study was the first to successfully disrupt BECN1 in MDA‑MB‑231 cells and to screen three stable monoclonal BECN1‑knockout cell lines, suggesting that BECN1‑knockout is not lethal in TNBC cells. Functional analysis revealed that complete loss of BECN1 suppressed MDA‑MB‑231 proliferation and colony formation via inducing G0/G1 cell cycle arrest, not apoptosis, in vitro. On the other hand, BECN1‑knockout inhibited the migratory and invasive ability of MDA‑MB‑231 cells by partially reversing signals of epithelial-mesenchymal transition. Finally, analysis of publicly available gene expression datasets revealed increased expression of BECN1 in TNBC samples. Taken togethe...Continue Reading

References

Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Nov 26, 2003·The Journal of Clinical Investigation·Xueping QuBeth Levine
Dec 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·Zhenyu YueNathaniel Heintz
Oct 20, 2005·The Biochemical Journal·Ofelia M Martínez-EstradaSenén Vilaró
Apr 5, 2007·Nature Protocols·Nicolaas A P FrankenChris van Bree
Feb 25, 2009·Nature Reviews. Cancer·Marcos Malumbres, Mariano Barbacid
Apr 2, 2010·Trends in Cell Biology·Sarah F FunderburkZhenyu Yue
Feb 12, 2011·Cell Death and Differentiation·R KangD Tang
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Jun 4, 2011·Cellular and Molecular Life Sciences : CMLS·Arun Satelli, Shulin Li
Aug 24, 2011·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Qing YaoLing Wang
Jan 5, 2013·Science·Le CongFeng Zhang
Jan 22, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Miao YuHua-chuan Zheng
Mar 13, 2013·EMBO Reports·Stéphane FrémontClarisse Berlioz-Torrent
May 21, 2013·Nature Cell Biology·Ryan C RussellKun-Liang Guan
May 25, 2013·The Journal of Biological Chemistry·Jie HanHannah Rabinowich
Oct 18, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yang ZhaoHua-chuan Zheng
Jan 10, 2014·Nature Reviews. Molecular Cell Biology·Guillermo MariñoGuido Kroemer
Jan 31, 2014·Molecular Cancer Research : MCR·Saurabh V LaddhaEileen White
May 17, 2014·World Journal of Gastroenterology : WJG·Zhao PengQiang Tong
May 20, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yuyu HeHonglei Chen
Apr 10, 2015·Nature Reviews. Genetics·Ophir ShalemFeng Zhang
Jun 5, 2015·Nature Reviews. Cancer·Francisco J Sánchez-Rivera, Tyler Jacks
Jan 13, 2016·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Hanan Al-Saeid Al-Shenawy

❮ Previous
Next ❯

Citations

Jul 17, 2020·OncoTargets and Therapy·Yang-Jie HuShui-Hong Zhou
Jun 21, 2020·Anti-cancer Agents in Medicinal Chemistry·Milad AshrafizadehAmirhossein Sahebkar

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.

CRISPR Ribonucleases Deactivation

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on mechanisms that underlie deactivation of CRISPR ribonucleases. Here is the latest research.

CRISPR Genome Editing & Therapy

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on the application of this system for gene editing and therapy in human diseases.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.

Parkinson's Disease & Autophagy (MDS)

Autophagy leads to degradation of damaged proteins and organelles by the lysosome. Impaired autophagy has been implicated in several diseases. Here is the role of autophagy in Parkinson’s disease.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.

Autophagy & Metabolism

Autophagy preserves the health of cells and tissues by replacing outdated and damaged cellular components with fresh ones. In starvation, it provides an internal source of nutrients for energy generation and, thus, survival. A powerful promoter of metabolic homeostasis at both the cellular and whole-animal level, autophagy prevents degenerative diseases. It does have a downside, however--cancer cells exploit it to survive in nutrient-poor tumors.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Breast Cancer Triple-N

Breast cancer cells have receptors for estrogen, progesterone, HER2 receptors (also called ERBB2). Triple-negative breast cancers do not have any of these receptors. Here are the latest discoveries pertaining to triple-negative breast cancers.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Breast Tumorigenesis

Breast tumorigenesis involves the production or formation of tumor(s) in breast tissue. Discover the latest research on breast tumorigenesis here.

CRISPR in Cancer

CRISPR-Cas system enables the editing of genes to create or correct mutations. Given that genome instability and mutation is one of the hallmarks of cancer, the CRISPR-Cas system is being explored to genetically alter and eliminate cancer cells. Here is the latest research.