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Review Open Access

Research progress on TMEM proteins in cancer progression and chemoresistance (Review)

  • Authors:
    • Ji Shi
    • Duo Zheng
    • Bing Yao
    • Qiang Liu
    • Huizhe Xu
    • Haozhe Piao
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China, Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110042, P.R. China, Department of Neurosurgery, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China, Central Laboratory Department, Liaoning Cancer Hospital and Institute/Cancer Hospital of Dalian University of Technology/Cancer Hospital of China Medical University, Shenyang, Liaoning 110042, P.R. China
    Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 219
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    Published online on: October 10, 2025
       https://doi.org/10.3892/ijmm.2025.5660
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Abstract

In cancer research, the transmembrane (TMEM) family of proteins has attracted considerable attention due to its role in tumor progression and chemoresistance. These membrane proteins are integral to cellular processes, including signal transduction, ion transport and cellular homeostasis, rendering them promising therapeutic targets. The TMEM proteins are implicated in several types of cancer, including breast, ovarian, lung and thyroid cancer, where they regulate numerous cellular processes, including proliferation, migration, invasion and survival. Notably, TMEM45A and TMEM158 contribute to resistance to platinum‑based chemotherapy by increasing the expression of proteins associated with hypoxic conditions and multidrug resistance. Additionally, epigenetic regulation, particularly promoter methylation of TMEM88, is pivotal in regulating TMEM88 expression and function in chemoresistance. The present review presents a systematic and comprehensive overview of the structural features, biological functions and regulatory mechanisms of key TMEM proteins across various types of cancer. It also highlights emerging connections between TMEM proteins and the tumor microenvironment, emphasizing their potential as promising therapeutic targets. The novel findings underscore the key role of the TMEM protein family in overcoming chemoresistance and lay a foundation for the development of targeted therapeutic strategies in cancer treatment.
View Figures

Figure 1

Classification of transmembrane
protein structures. (A) Single-pass membrane protein, the lipid
bilayer is traversed by the polypeptide chain via a single α-helix.
(B) A number of transmembrane proteins are predominantly situated
on the cytoplasmic side of the lipid bilayer. (C) Multi-membrane
protein, the lipid bilayer is traversed by the polypeptide chain
via two or more α-helix. (D) Some transmembrane proteins form large
ion channels by transversing the plasma membrane with multiple
β-folded sheets.

Figure 2

Classification of transmembrane
family functions. (A) GPCRs mediate cellular responses by
activating intracellular signaling pathways through G-proteins upon
ligand binding. (B) Ion channels allow the passive flow of ions
across the membrane, essential for processes such as nerve
transmission and muscle contraction. (C) Transporter proteins
actively move molecules across the membrane, often against
concentration gradients, to maintain cellular homeostasis. (D)
Receptors bind specific molecules to initiate cellular responses,
influencing processes such as immune function, cell growth and
metabolism. GPCR, G protein-coupled receptor.

Figure 3

List of TMEM protein structures.
Representative schematic diagrams of 16 TMEM proteins, TMEM7,
TMEM25, TMEM16A, TMEM45A, TMEM45B, TMEM48, TMEM65, TMEM88,
TMEM106A, TMEM140, TMEM158, TMEM159, TMEM173, TMEM176A, TMEM176B
and TMEM205, illustrating their predicted transmembrane structures,
subcellular localization and classification as single-pass or
multi-pass membrane proteins. TMEM, transmembrane.

Figure 4

Roles and functions of TMEMs in
cancer development, immune response and cellular regulation,
providing a view of their functions across different pathways.
TMEM, transmembrane; EMT, epithelial-mesenchymal transition; DVL,
Dishevelled.
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Copy and paste a formatted citation
Spandidos Publications style
Shi J, Zheng D, Yao B, Liu Q, Xu H and Piao H: Research progress on TMEM proteins in cancer progression and chemoresistance (Review). Int J Mol Med 56: 219, 2025.
APA
Shi, J., Zheng, D., Yao, B., Liu, Q., Xu, H., & Piao, H. (2025). Research progress on TMEM proteins in cancer progression and chemoresistance (Review). International Journal of Molecular Medicine, 56, 219. https://doi.org/10.3892/ijmm.2025.5660
MLA
Shi, J., Zheng, D., Yao, B., Liu, Q., Xu, H., Piao, H."Research progress on TMEM proteins in cancer progression and chemoresistance (Review)". International Journal of Molecular Medicine 56.6 (2025): 219.
Chicago
Shi, J., Zheng, D., Yao, B., Liu, Q., Xu, H., Piao, H."Research progress on TMEM proteins in cancer progression and chemoresistance (Review)". International Journal of Molecular Medicine 56, no. 6 (2025): 219. https://doi.org/10.3892/ijmm.2025.5660
Copy and paste a formatted citation
x
Spandidos Publications style
Shi J, Zheng D, Yao B, Liu Q, Xu H and Piao H: Research progress on TMEM proteins in cancer progression and chemoresistance (Review). Int J Mol Med 56: 219, 2025.
APA
Shi, J., Zheng, D., Yao, B., Liu, Q., Xu, H., & Piao, H. (2025). Research progress on TMEM proteins in cancer progression and chemoresistance (Review). International Journal of Molecular Medicine, 56, 219. https://doi.org/10.3892/ijmm.2025.5660
MLA
Shi, J., Zheng, D., Yao, B., Liu, Q., Xu, H., Piao, H."Research progress on TMEM proteins in cancer progression and chemoresistance (Review)". International Journal of Molecular Medicine 56.6 (2025): 219.
Chicago
Shi, J., Zheng, D., Yao, B., Liu, Q., Xu, H., Piao, H."Research progress on TMEM proteins in cancer progression and chemoresistance (Review)". International Journal of Molecular Medicine 56, no. 6 (2025): 219. https://doi.org/10.3892/ijmm.2025.5660
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