# SMURF1 Downregulation Highlights Its Potential Role in Breast Cancer

**Authors:** Leyla Tekin, Funda Dinç, Cenk Yazkan, Murat Cenik, Çilem Özdemir, Onur Amaç, Tuba Edgünlü

PMC · DOI: 10.3390/ijms27041921 · International Journal of Molecular Sciences · 2026-02-17

## TL;DR

This study finds that SMURF1 is less active in breast cancer tissues, suggesting it may help prevent tumor growth.

## Contribution

The study identifies SMURF1 downregulation in breast cancer and links it to Wnt/β-catenin signaling.

## Key findings

- SMURF1 mRNA is significantly downregulated in breast cancer tissues compared to normal tissues.
- SMURF1 interacts with proteins in TGF-β/BMP and Wnt/β-catenin pathways, suggesting roles in tumor progression.
- Downregulation of SMURF1 may enhance Wnt/β-catenin signaling activity in breast cancer.

## Abstract

This study aimed to evaluate the mRNA and protein levels of SMURF1 and SMURF2 in breast cancer and to elucidate their potential biological roles through in silico analyses. Tumor and adjacent normal tissue samples were collected from 30 newly diagnosed breast cancer patients who underwent mastectomy. The mRNA expression levels of SMURF1 and SMURF2 were analyzed by quantitative PCR (qPCR), and their protein expression patterns were evaluated using immunohistochemistry (IHC). In addition, protein–protein interaction (PPI) and functional enrichment analyses were performed via the STRING database to identify potential molecular interactions and biological pathways associated with these genes. The mRNA expression level of SMURF1 was significantly downregulated in tumor tissues compared to normal breast tissues (p = 0.002), whereas no significant difference was observed in SMURF2 mRNA expression (p = 0.981). IHC results revealed that SMURF1 and SMURF2 protein levels did not differ significantly between tumor and normal samples. The in silico analysis demonstrated that SMURF1 and SMURF2 interact with multiple proteins involved in key signaling pathways, particularly the TGF-β/BMP and Wnt/β-catenin pathways. The findings suggest that the downregulation of SMURF1 in breast cancer may contribute to tumor progression by enhancing Wnt/β-catenin signaling activity. The interactions of SMURF1 and SMURF2 with TGF-β/BMP pathway regulators indicate that these genes may play dual roles in both tumor-suppressive and oncogenic mechanisms, depending on the cellular context.

## Linked entities

- **Genes:** SMURF1 (SMAD specific E3 ubiquitin protein ligase 1) [NCBI Gene 57154], SMURF2 (SMAD specific E3 ubiquitin protein ligase 2) [NCBI Gene 64750]
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** TCF4 (transcription factor 4) [NCBI Gene 6925] {aka CDG2T, E2-2, FCD2, FECD3, ITF-2, ITF2}, RPS6KB1 (ribosomal protein S6 kinase B1) [NCBI Gene 6198] {aka PS6K, S6K, S6K-beta-1, S6K1, STK14A, p70 S6KA}, AXIN1 (axin 1) [NCBI Gene 8312] {aka AXIN, CMDOH, PPP1R49}, ACTB (actin beta) [NCBI Gene 60] {aka BKRNS, BNS, BRWS1, CSMH, DDS1, PS1TP5BP1}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, SMAD6 (SMAD family member 6) [NCBI Gene 4091] {aka AOVD2, HsT17432, MADH6, MADH7}, AR (androgen receptor) [NCBI Gene 367] {aka AIS, AR8, DHTR, HPCX3, HUMARA, HYSP1}, SMAD1 (SMAD family member 1) [NCBI Gene 4086] {aka BSP-1, BSP1, JV4-1, JV41, MADH1, MADR1}, SMAD5 (SMAD family member 5) [NCBI Gene 4090] {aka DWFC, JV5-1, MADH5}, COP1 (COP1 E3 ubiquitin ligase) [NCBI Gene 64326] {aka CFAP78, FAP78, RFWD2, RNF200}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, RPS27A (ribosomal protein S27a) [NCBI Gene 6233] {aka CEP80, HEL112, S27A, UBA80, UBCEP1, UBCEP80}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, TOP2A (DNA topoisomerase II alpha) [NCBI Gene 7153] {aka TOP2, TOP2alpha, TOPIIA, TP2A}, EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, TGFBR2 (transforming growth factor beta receptor 2) [NCBI Gene 7048] {aka AAT3, FAA3, LDS1B, LDS2, LDS2B, MFS2}, YY1 (YY1 transcription factor) [NCBI Gene 7528] {aka DELTA, GADEVS, INO80S, NF-E1, UCRBP, YIN-YANG-1}, SMAD2 (SMAD family member 2) [NCBI Gene 4087] {aka CHTD8, JV18, JV18-1, LDS6, MADH2, MADR2}, SMURF1 (SMAD specific E3 ubiquitin protein ligase 1) [NCBI Gene 57154], MYL2 (myosin light chain 2) [NCBI Gene 4633] {aka CMH10, MFM12, MLC-2, MLC-2s/v, MLC-2v, MLC2}, RUNX2 (RUNX family transcription factor 2) [NCBI Gene 860] {aka AML3, CBF-alpha-1, CBFA1, CCD, CCD1, CLCD}, SMAD3 (SMAD family member 3) [NCBI Gene 4088] {aka HSPC193, HsT17436, JV15-2, LDS1C, LDS3, MADH3}, BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672] {aka BRCAI, BRCC1, BROVCA1, FANCS, IRIS, PNCA4}, SMURF2 (SMAD specific E3 ubiquitin protein ligase 2) [NCBI Gene 64750], BTRC (beta-transducin repeat containing E3 ubiquitin protein ligase) [NCBI Gene 8945] {aka BETA-TRCP, FBW1A, FBXW1, FBXW1A, FWD1, bTrCP}, SRSF5 (serine and arginine rich splicing factor 5) [NCBI Gene 6430] {aka HRS, SFRS5, SRP40}, RHOA (ras homolog family member A) [NCBI Gene 387] {aka ARH12, ARHA, EDFAOB, RHO12, RHOH12}, TGFBR1 (transforming growth factor beta receptor 1) [NCBI Gene 7046] {aka AAT5, ACVRLK4, ALK-5, ALK5, ESS1, LDS1}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, USP15 (ubiquitin specific peptidase 15) [NCBI Gene 9958] {aka UNPH-2, UNPH4}, LRP6 (LDL receptor related protein 6) [NCBI Gene 4040] {aka ADCAD2, EVR8, OPTA4, STHAG7}, EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) [NCBI Gene 2146] {aka ENX-1, ENX1, EZH2b, KMT6, KMT6A, WVS}, MCAM (melanoma cell adhesion molecule) [NCBI Gene 4162] {aka CD146, HEMCAM, METCAM, MUC18, MelCAM}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, TRIB2 (tribbles pseudokinase 2) [NCBI Gene 28951] {aka C5FW, GS3955, TRB2}, BMP1 (bone morphogenetic protein 1) [NCBI Gene 649] {aka OI13, PCOLC, PCP, TLD}, UBE2L3 (ubiquitin conjugating enzyme E2 L3) [NCBI Gene 7332] {aka E2-F1, L-UBC, UBCH7, UbcM4}, SMAD7 (SMAD family member 7) [NCBI Gene 4092] {aka CRCS3, MADH7, MADH8}, UBC (ubiquitin C) [NCBI Gene 7316] {aka HMG20}, KLF5 (KLF transcription factor 5) [NCBI Gene 688] {aka BTEB2, CKLF, IKLF}, RNF20 (ring finger protein 20) [NCBI Gene 56254] {aka BRE1, BRE1A, hBRE1}, MUL1 (mitochondrial E3 ubiquitin protein ligase 1) [NCBI Gene 79594] {aka C1orf166, GIDE, MAPL, MULAN, RNF218}
- **Diseases:** Tumor (MESH:D009369), carcinoma in situ (MESH:D002278), esophageal squamous cell carcinoma (MESH:D000077277), injury to (MESH:D014947), bone metastasis (MESH:D009362), carcinogenic (MESH:D011230), colorectal, lung, and gastric cancers (MESH:D015179), HCC (MESH:D006528), PNI (MESH:D052958), invasion (MESH:D009361), gastric cancer (MESH:D013274), Breast Cancer (MESH:D001943), tumorigenesis (MESH:D063646)
- **Chemicals:** poly-L-lysine (-), paraffin (MESH:D010232), H&amp;E (MESH:D006371), hematoxylin (MESH:D006416), eosin (MESH:D004801), formalin (MESH:D005557), SYBR Green (MESH:C098022), TRIzol (MESH:C411644)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** NGMM007 — Homo sapiens (Human), Induced pluripotent stem cell (CVCL_A4DH)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12941280/full.md

## References

27 references — full list in the complete paper: https://tomesphere.com/paper/PMC12941280/full.md

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Source: https://tomesphere.com/paper/PMC12941280