OTUD7B suppresses Smac mimetic-induced lung cancer cell invasion and migration via deubiquitinating TRAF3.

Journal of Experimental & Clinical Cancer Research : CR
Boxiang ZhangSida Qin

Abstract

Smac mimetics are a type of drug that can induce apoptosis by antagonizing IAP family members in cancer treatment. However, a recent study showed that Smac mimetics can trigger cell invasion and migration in cancer cells by activating the NF-κB pathway. We assessed lung cancer cell elongation, invasion and migration under treatment with the Smac mimetic LCL161. Functional analyses (in vitro and in vivo) were performed to detect the contribution of NIK and OTUD7B to LCL161-induced cell invasion and migration. The role of OTUD7B in regulation of the TRAF3/NIK/NF-κB pathway under LCL161 treatment was analysed by immunoblotting, immunoprecipitation, luciferase and ubiquitin assays, shRNA silencing and plasmid overexpression. Expression levels of OTUD7B, NIK and TRAF3 in tissue samples from lung cancer patients were examined by immunohistochemistry. We found that LCL161 stimulates lung cancer cell elongation, invasion and migration at non-toxic concentrations. Mechanistically, LCL161 results in NIK accumulation and activates the non-canonical rather than the canonical NF-κB pathway to enhance the transcription of target genes, such as IL-2 and MMP-9. Importantly, knockdown of NIK dramatically suppresses LCL161-induced cell invasion ...Continue Reading

References

Feb 5, 2010·Cancer Cell·Swarna MehrotraDario C Altieri
Apr 13, 2010·Nature Reviews. Cancer·Sarah G Hymowitz, Ingrid E Wertz
Jul 24, 2010·Nature Reviews. Cancer·Mads Gyrd-Hansen, Pascal Meier
Oct 27, 2010·Cancer Letters·Milind M PoreFrank A E Kruyt
Dec 21, 2010·Oncogene·M M ChaturvediB B Aggarwal
Dec 22, 2010·Cell Research·Shao-Cong Sun
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Nov 26, 2011·The EMBO Journal·Tripat Kaur OberoiKrishnaraj Rajalingam
Feb 2, 2012·Nature Reviews. Drug Discovery·Simone Fulda, Domagoj Vucic
Jun 8, 2013·Circulation Research·Jun-ichi Abe, Bradford C Berk
Aug 13, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jeffrey R InfanteRoger B Cohen
Sep 16, 2014·International Journal of Cancer. Journal International Du Cancer·Jacques FerlayFreddie Bray
Sep 4, 2015·Molecular Cancer Therapeutics·Ravi K AmaravadiAlex A Adjei
Jan 15, 2016·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Peter GoldstrawUNKNOWN International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee Advisory Boards and Particip
Mar 29, 2016·Cancer Metastasis Reviews·Helmut H Popper
Oct 16, 2016·Journal of Experimental & Clinical Cancer Research : CR·Chengcheng YangSida Qin
Jan 1, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Adeeb DerakhshanCarter Van Waes
May 29, 2018·Immunotherapy·Stephanie K Dougan, Michael Dougan
Sep 21, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Aditya BardiaSung-Bae Kim
Jan 9, 2019·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Jan 18, 2019·Cancer Immunology Research·Jessica MichieJane Oliaro

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
flow cytometry
PCR
ubiquitination
nuclear translocation
co-immunoprecipitation
deubiquitination
not

Software Mentioned

GraphPad
ImageJ
GraphPad Prism
R

Related Concepts

Related Feeds

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.

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.

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

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.