Related Experiment Video

Updated: Dec 30, 2025

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells
09:10

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells

Published on: October 28, 2019

7.6K

NEK2 induces autophagy-mediated bortezomib resistance by stabilizing Beclin-1 in multiple myeloma

Jiliang Xia1,2, Yanjuan He1, Bin Meng2

  • 1Department of Hematology, Xiangya Hospital, Central South University, Changsha, China.

Molecular Oncology
|January 20, 2020
PubMed

Insights

High NEK2 levels promote drug resistance in multiple myeloma (MM) by enhancing autophagy. Inhibiting autophagy with chloroquine (CQ) alongside bortezomib (BTZ) can overcome this resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • The protein kinase NEK2 is implicated in drug resistance across various cancers.
  • Elevated NEK2 expression correlates with poorer survival outcomes in multiple myeloma (MM).
  • Understanding NEK2's role in MM drug resistance mechanisms is crucial for developing effective therapies.

Purpose of the Study:

  • To elucidate the mechanism by which NEK2 confers drug resistance in multiple myeloma.
  • To investigate the role of autophagy in NEK2-mediated drug resistance.
  • To evaluate the therapeutic potential of combining autophagy inhibitors with chemotherapy.

Main Methods:

  • Investigated the effect of NEK2 on autophagy in MM cells.
  • Assessed the impact of NEK2 on Beclin-1 protein stability and ubiquitination.
  • Utilized gene knockdown techniques for NEK2, Beclin-1, and USP7.
  • Evaluated the efficacy of combining chloroquine (CQ) and bortezomib (BTZ) in vitro and in vivo.

Main Results:

  • NEK2 enhances autophagy in MM cells.
  • NEK2 binds and stabilizes Beclin-1 protein, decreasing its ubiquitination via interaction with USP7.
  • Knockdown of Beclin-1 abrogates NEK2-induced autophagy and sensitizes MM cells to bortezomib.
  • Combined CQ and BTZ treatment effectively overcomes NEK2-induced drug resistance.

Conclusions:

  • A novel mechanism involving the NEK2/USP7/Beclin-1 complex activating autophagy in MM cells is identified.
  • Targeting the autophagy signaling pathway presents a promising strategy to combat NEK2-driven drug resistance in MM.
  • This study provides a rationale for combining autophagy inhibitors with standard chemotherapy for MM treatment.
Keywords:
Beclin-1NEK2autophagymultiple myelomaubiquitination

More Related Videos

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells09:51

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells

Published on: June 30, 2023

1.3K
Cell Subtype-specific Analysis of Neuronal Membrane Proteasome in Somatosensory Neurons09:27

Cell Subtype-specific Analysis of Neuronal Membrane Proteasome in Somatosensory Neurons

Published on: October 10, 2025

372

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.5K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
8.1K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
4.2K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.7K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
5.6K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.6K