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Unveiling the Role of Inner Membrane Protein in Breast Cancer Metastasis

A better understanding of the novel protein’s role in promoting breast cancer cell migration and survival presents a potential therapeutic strategy against this disease.

The nuclear envelope is made of outer and inner membranes that are separated by the perinuclear space and joined at nuclear pore complexes. Proteins on the inner membrane are known to play important roles in cell cycle regulation, DNA repair, ageing, and cell migration of tumour formation and progression. However, while many inner membrane proteins have been discovered in proteomic studies recently, the specific proteins and protein-based mechanisms contributing towards cancer pathogenesis remain to be studied.

A study published in the journal Oncogene has revealed a novel inner membrane transmembrane protein 201 (TMEM201) that advances breast cancer metastasis.

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among females worldwide. Metastasis, or the process by which cancer cells spread to other parts of the body, is the main cause of death in breast cancer patients. Especially with triple-negative breast cancer, its propensity for aggressive metastasis and lack of estrogen receptor, progesterone receptor, and HER2 receptor makes it ineligible for hormone or anti-HER2 therapy. Hence, a team led by Li Jia from the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences set out to understand the mechanisms governing the development and malignancy of triple-negative breast cancers.

To identify nuclear envelope proteins that regulate triple-negative breast cancers, the research team screened 296 candidate nuclear envelope proteins based on the Gene Ontology database. Further screening found that a high expression of TMEM201 was correlated with poor prognosis and that TMEM201 expression was elevated in triple-negative breast cancer patients compared to non-triple-negative breast cancer patients.

Through overexpression studies and RNA sequencing and analysis, the team found that increased expression of TMEM201 promoted TGFβ-mediated epithelial-to-mesenchymal transition (EMT), thereby aiding in the migration, invasion, survival of breast cancer cells. Furthermore, the team demonstrated that TMEM201 physically interacted with SMAD2/3 and was needed for the phosphorylation of SMAD2/3, nuclear translocation, and transcriptional activation of TGFβ.

Together, these results explain the role of a specific inner membrane protein in the metastasis of aggressive breast cancer and present a potential therapeutic strategy for this poor-prognosis disease. [APBN]

Source: Kong et al. (2021). Inner nuclear membrane protein TMEM201 promotes breast cancer metastasis by positive regulating TGFβsignaling. Oncogene, 1-10.