# Telomeric Ends and Telomerase—Canonical and Non-Canonical Roles in Breast Cancer Tumorigenesis and Therapy Resistance

**Authors:** Magdalena Kostrzewa, Julia Niedzielska, Wiktoria Mieczkowska, Maja Hoffmann, Julia Rypińska, Adrianna Kowalczyk, Magdalena Stachowiak, Błażej Rubiś

PMC · DOI: 10.3390/biomedicines14020314 · Biomedicines · 2026-01-30

## TL;DR

This paper explores how telomerase, known for maintaining telomeres, also plays non-canonical roles in breast cancer development and resistance to treatment.

## Contribution

The paper provides a comprehensive summary of telomerase's canonical and non-canonical roles in breast cancer tumorigenesis and therapy resistance.

## Key findings

- Telomerase's non-canonical roles in mitochondrial and epigenetic processes contribute to cancer cell survival.
- Understanding telomerase's multifaceted mechanisms can lead to new therapeutic strategies for breast cancer.
- Telomerase overexpression in adulthood is linked to cancer progression and resistance to chemotherapy.

## Abstract

Telomerase is known as a very specific marker of embryonic cells. It is responsible for telomere elongation (bypassing the end-replication problem) and thus supports normal cell division during tissue and organ development. But it is generally absent or very low in most normal adult somatic cells. However, its overexpression in adulthood (due to secondary expression and activity restoration) is commonly known to be associated with cancer. Apart from its canonical function (associated with telomere length restoration), it also carries out various other roles. Its non-canonical activity covers mitochondrial and epigenetic processes. Consequently, it contributes to the cell response to stress and chemotherapeutic drug treatment. A more detailed understanding of these phenomena offers the opportunity to identify new pathways and targets that may serve as critical factors in breast cancer diagnostics and therapy. In this article, we summarize the latest reports on the discovery of telomerase’s nature, including its canonical and non-canonical roles. The manuscript highlights how these mechanisms contribute to tumorigenesis, therapy resistance, and the survival of cancer cells. Understanding these multifaceted mechanisms behind hTERT’s role in (breast) cancer progression and therapy resistance is crucial for developing more effective therapeutic strategies.

## Linked entities

- **Proteins:** tert.L (telomerase reverse transcriptase L homeolog)
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, TINF2 (TERF1 interacting nuclear factor 2) [NCBI Gene 26277] {aka DKCA3, DKCA5, TIN2}, BRCA2 (BRCA2 DNA repair associated) [NCBI Gene 675] {aka BRCC2, BROVCA2, FACD, FAD, FAD1, FANCD}, TERF2IP (TERF2 interacting protein) [NCBI Gene 54386] {aka DRIP5, RAP1}, CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}, STING1 (stimulator of interferon response cGAMP interactor 1) [NCBI Gene 340061] {aka ERIS, MITA, MPYS, NET23, SAVI, STING}, SOD2 (superoxide dismutase 2) [NCBI Gene 6648] {aka GC1, GClnc1, IPO-B, IPOB, MNSOD, MVCD6}, AURKB (aurora kinase B) [NCBI Gene 9212] {aka AIK2, AIM-1, AIM1, ARK-2, ARK2, AurB}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, TERF2 (telomeric repeat binding factor 2) [NCBI Gene 7014] {aka TRBF2, TRF2}, PTPN11 (protein tyrosine phosphatase non-receptor type 11) [NCBI Gene 5781] {aka BPTP3, CFC, JMML, METCDS, NS1, PTP-1D}, TEAD4 (TEA domain transcription factor 4) [NCBI Gene 7004] {aka EFTR-2, RTEF1, TCF13L1, TEF-3, TEF3, TEFR-1}, IGFBP3 (insulin like growth factor binding protein 3) [NCBI Gene 3486] {aka BP-53, IBP-3, IBP3, IGFBP-3}, H3P16 (H3 histone pseudogene 16) [NCBI Gene 644914] {aka H3.6, H3F3AP6, p21}, POT1 (protection of telomeres 1) [NCBI Gene 25913] {aka CMM10, CRMCC3, GLM9, HPOT1, PFBMFT8, TPDS3}, DNMT1 (DNA methyltransferase 1) [NCBI Gene 1786] {aka ADCADN, AIM, CXXC9, DNMT, HSN1E, MCMT}, TERT (telomerase reverse transcriptase) [NCBI Gene 7015] {aka CMM9, DKCA2, DKCB4, EST2, PFBMFT1, TCS1}, ATM (ATM serine/threonine kinase) [NCBI Gene 472] {aka AT1, ATA, ATC, ATD, ATDC, ATE}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, SRC (SRC proto-oncogene, non-receptor tyrosine kinase) [NCBI Gene 6714] {aka ASV, SRC1, THC6, c-SRC, p60-Src}, TERF1 (telomeric repeat binding factor 1) [NCBI Gene 7013] {aka PIN2, TRBF1, TRF, TRF1, hTRF1-AS, t-TRF1}, EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, TEP1 (telomerase associated protein 1) [NCBI Gene 7011] {aka TLP1, TP1, TROVE1, VAULT2, p240}, ESR2 (estrogen receptor 2) [NCBI Gene 2100] {aka ER-BETA, ESR-BETA, ESRB, ESTRB, Erb, NR3A2}, TPP1 (tripeptidyl peptidase 1) [NCBI Gene 1200] {aka CLN2, GIG1, LPIC, SCAR7, TPP-1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, CAT (catalase) [NCBI Gene 847], HDAC9 (histone deacetylase 9) [NCBI Gene 9734] {aka HD7, HD7b, HD9, HDAC, HDAC7B, HDAC9B}, MARCHF8 (membrane associated ring-CH-type finger 8) [NCBI Gene 220972] {aka CMIR, MARCH-VIII, MARCH8, MIR, RNF178, c-MIR}, IGH (immunoglobulin heavy locus) [NCBI Gene 3492] {aka IGD1, IGH.1@, IGH@, IGHD@, IGHDY1, IGHJ}, TERC (telomerase RNA component) [NCBI Gene 7012] {aka DKCA1, PFBMFT2, SCARNA19, TER, TR, TRC3}
- **Diseases:** B-cell neoplasms (MESH:D016393), lung and gastric cancer (MESH:D013274), Breast Cancer (MESH:D001943), TNBC (MESH:D064726), telomere dysfunction (MESH:C536801), Tumorigenesis (MESH:D063646), oncological diseases (MESH:D000072716), acute myeloid leukemia (MESH:D015470), hepatocellular carcinoma (MESH:D006528), prostate (MESH:D011472), solid (MESH:D018250), head and neck squamous cell carcinoma (MESH:D000077195), glioblastoma (MESH:D005909), breast, prostate, non-small-cell lung cancer (MESH:D002289), ALM (MESH:D008545), metastasis (MESH:D009362), neurodegenerative diseases (MESH:D019636), injury to (MESH:D014947), chronic lymphocytic leukemia (MESH:D015451), mitochondrial dysfunction (MESH:D028361), death (MESH:D003643), acute lymphoblastic leukemia (MESH:D054198), infertility (MESH:D007246), cancer (MESH:D009369), cytotoxic (MESH:D064420)
- **Chemicals:** glutathione (MESH:D005978), telomestatin (MESH:C431888), L- (MESH:D007930), Cytosine (MESH:D003596), genistein (MESH:D019833), TSA (MESH:C012589), OH (MESH:C031356), BPA (MESH:C006780), ICI 182,780 (MESH:D000077267), PBS (MESH:D007854), oligonucleotide (MESH:D009841), hydroxyl radical (MESH:D017665), B19 (MESH:C454064), ROS (MESH:D017382), 5-aza-2'-deoxycytidine (MESH:D000077209), 5-azacytidine (MESH:D001374), helenalin (MESH:C001329), bevacizumab (MESH:D000068258), curcumin (MESH:D003474), GRN163L (MESH:C519562), BioRender (-), O2- (MESH:D013481), BPS (MESH:C543008), H2O2 (MESH:D006861), porphyrin (MESH:D011166), cisplatin (MESH:D002945), 6-thio-2'-deoxyguanosine (MESH:C002062), BPF (MESH:C000611646), SiO2 (MESH:D012822), BIBR1532 (MESH:C458523), ATRA (MESH:D014212), paclitaxel (MESH:D017239), Boldine (MESH:C011686), Tam (MESH:D013629), 17beta-estradiol (MESH:D004958), peroxide (MESH:D010545), KML-001 (MESH:C017947), Carbon (MESH:D002244), tigecycline (MESH:D000078304), G4 (MESH:D004003), AZD1152 (MESH:C520647), PDS (MESH:C567962), TMPyP4 (MESH:C021096), Herceptin (MESH:D000068878), centchroman (MESH:D002486), MST-312 (MESH:C470197), RHPS4 (MESH:C438609)
- **Species:** Curcuma longa (turmeric, species) [taxon 136217], Peumus boldus (species) [taxon 63812], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** ZR75.1 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0588), 21NT — Homo sapiens (Human), Breast carcinoma, Cancer cell line (CVCL_7933), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031), SK-BR-3 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0033), MDA-MB-231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062), T47D — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0553)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12937728/full.md

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12937728/full.md

## References

104 references — full list in the complete paper: https://tomesphere.com/paper/PMC12937728/full.md

---
Source: https://tomesphere.com/paper/PMC12937728