# Biomechanical Forces in Prostate Cancer: Current Insights and Future Directions

**Authors:** Yunjie Ju, Dong Ni, Shimin Zou, Ping Dai, Jianhu Xie, Kangnan He, Yarong Song, Yifei Xing, Liang Chen

PMC · DOI: 10.3390/cancers18040608 · Cancers · 2026-02-12

## TL;DR

This review explores how mechanical forces in the prostate cancer environment influence tumor behavior and treatment, and how understanding these forces could lead to new therapies.

## Contribution

The paper synthesizes recent advances in prostate cancer biomechanics and proposes integrating mechanical insights into diagnosis and treatment strategies.

## Key findings

- Malignant prostate tissue is stiffer than benign tissue.
- Prostate cancer cells adapt to mechanical changes through force-responsive signaling pathways.
- Mechanical adaptations may contribute to therapy resistance and metastatic colonization.

## Abstract

Prostate cancer evolves within a mechanically dynamic microenvironment shaped by extracellular matrix remodeling, tissue stiffness, solid stress, and fluid flow. Increasing evidence indicates that these biomechanical cues regulate tumor cell survival, invasion, metastatic colonization, and therapeutic response through mechanotransduction pathways. In this review, we summarize recent advances in prostate cancer biomechanics and discuss how integrating mechanical insights may improve diagnosis, risk stratification, and treatment strategies. Understanding force-related vulnerabilities may also facilitate the development of emerging “mechanotherapies” for prostate cancer.

Over the past decade, research in tumor biomechanics has increasingly shown that cancer cells adapt to changing physical microenvironments by rewiring adhesion, cytoskeletal organization, and force-responsive signaling pathways, thereby shaping survival, invasion, and responses to therapy. Prostate cancer (PCa), like other solid tumors, resides in a highly dynamic mechanical milieu molded by extracellular matrix (ECM) remodeling, solid stress, and fluid shear forces. Available evidence generally supports that malignant prostate tissue is stiffer than benign tissue. During metastatic progression, however, the mechanical phenotype of PCa cells appears to undergo context-dependent remodeling. Such mechanical adaptations may help tumor cells withstand the physical challenges associated with circulation, adhesion switching, and colonization, and may intersect with the development of therapy resistance. Here, we synthesize recent advances in PCa biomechanics, highlight the intricate interplay between mechanical cues and tumor biology, and discuss opportunities to incorporate a mechanical perspective into diagnostic and therapeutic strategies. A deeper understanding of these processes may ultimately enable the development of emerging “mechanotherapies” for prostate cancer.

## Linked entities

- **Diseases:** prostate cancer (MONDO:0005159)

## Full-text entities

- **Genes:** YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, CCN2 (cellular communication network factor 2) [NCBI Gene 1490] {aka CTGF, HCS24, IBP-8, IGFBP8, KMD, NOV2}, RHOA (ras homolog family member A) [NCBI Gene 387] {aka ARH12, ARHA, EDFAOB, RHO12, RHOH12}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, USP8 (ubiquitin specific peptidase 8) [NCBI Gene 9101] {aka HumORF8, PITA4, SPG59, UBPY}, AMOTL2 (angiomotin like 2) [NCBI Gene 51421] {aka LCCP}, CASP9 (caspase 9) [NCBI Gene 842] {aka APAF-3, APAF3, ICE-LAP6, MCH6, PPP1R56}, CFL1 (cofilin 1) [NCBI Gene 1072] {aka CFL, HEL-S-15, cofilin}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, LAMB2 (laminin subunit beta 2) [NCBI Gene 3913] {aka LAMS, NPHS5, PIERS}, B3gnt9 (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 9) [NCBI Gene 97440] {aka 3-Gn-T9, B3gnt9-ps, BGnT-9, beta-1, beta3Gn-T9}, AR (androgen receptor) [NCBI Gene 367] {aka AIS, AR8, DHTR, HPCX3, HUMARA, HYSP1}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, TNC (tenascin C) [NCBI Gene 3371] {aka 150-225, DFNA56, GMEM, GP, HXB, JI}, TAFAZZIN (tafazzin, phospholipid-lysophospholipid transacylase) [NCBI Gene 6901] {aka BTHS, CMD3A, EFE, EFE2, G4.5, LVNCX}, EPHB2 (EPH receptor B2) [NCBI Gene 2048] {aka BDPLT22, CAPB, DRT, EK5, EPHT3, ERK}, SPP1 (secreted phosphoprotein 1) [NCBI Gene 6696] {aka BNSP, BSPI, ETA-1, OPN}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}, TNFSF10 (TNF superfamily member 10) [NCBI Gene 8743] {aka APO2L, Apo-2L, CD253, TANCR, TL2, TNLG6A}, PIEZO1 (piezo type mechanosensitive ion channel component 1 (Er blood group)) [NCBI Gene 9780] {aka DHS, ER, FAM38A, LMPH3, LMPHM6, Mib}, Twf1 (twinfilin actin binding protein 1) [NCBI Gene 19230] {aka A6, Ptk9, twinfilin}, SRC (SRC proto-oncogene, non-receptor tyrosine kinase) [NCBI Gene 6714] {aka ASV, SRC1, THC6, c-SRC, p60-Src}, KDR (kinase insert domain receptor) [NCBI Gene 3791] {aka CD309, FLK1, VEGFR, VEGFR2}, UBTD1 (ubiquitin domain containing 1) [NCBI Gene 80019], Bhlhe23 (basic helix-loop-helix family, member e23) [NCBI Gene 140489] {aka A930001L02Rik, BETA4, Beta3b, Bhlhb4}, LOX (lysyl oxidase) [NCBI Gene 4015] {aka AAT10}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, BTRC (beta-transducin repeat containing E3 ubiquitin protein ligase) [NCBI Gene 8945] {aka BETA-TRCP, FBW1A, FBXW1, FBXW1A, FWD1, bTrCP}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, MMRN1 (multimerin 1) [NCBI Gene 22915] {aka ECM, EMILIN4, GPIa*, MMRN}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, LIMK1 (LIM domain kinase 1) [NCBI Gene 3984] {aka LIMK, LIMK-1}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, NBR1 (NBR1 autophagy cargo receptor) [NCBI Gene 4077] {aka 1A1-3B, IAI3B, M17S2, MIG19}, RHO (rhodopsin) [NCBI Gene 6010] {aka CSNBAD1, OPN2, RP4}, ITGB1 (integrin subunit beta 1) [NCBI Gene 3688] {aka CD29, FNRB, GPIIA, MDF2, MSK12, VLA-BETA}, Itgb1 (integrin beta 1 (fibronectin receptor beta)) [NCBI Gene 16412] {aka 4633401G24Rik, CD29, Fnrb, Gm9863, gpIIa}, ANKRD1 (ankyrin repeat domain 1) [NCBI Gene 27063] {aka ALRP, C-193, CARP, CVARP, MCARP, bA320F15.2}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, PTK2 (protein tyrosine kinase 2) [NCBI Gene 5747] {aka FADK, FADK 1, FAK, FAK1, FRNK, PPP1R71}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, Ugt1a6b (UDP glucuronosyltransferase 1 family, polypeptide A6B) [NCBI Gene 394435] {aka A9', Ugt1a9}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, ITGAV (integrin subunit alpha V) [NCBI Gene 3685] {aka CD51, IDNDC, MSK8, VNRA, VTNR}
- **Diseases:** hypoxia (MESH:D000860), CRPC (MESH:D064129), hypoxic (MESH:D002534), PIN (MESH:D019048), Cancer (MESH:D009369), adenocarcinoma (MESH:D000230), rectal cancer (MESH:D012004), fibrosis (MESH:D005355), GBM (MESH:D005910), PCa (MESH:D011471), HA (MESH:C565742), injury to (MESH:D014947), pancreatic cancer (MESH:D010190), glioblastoma (MESH:D005909), lymph node metastasis (MESH:D008207), benign prostatic hyperplasia (MESH:D011470), toxicity (MESH:D064420), bone metastasis (MESH:D009362), tumorigenic (MESH:D002471)
- **Chemicals:** 4-MU (MESH:D006923), HA (MESH:D006820), bevacizumab (MESH:D000068258), water (MESH:D014867), imatinib (MESH:D000068877), losartan (MESH:D019808), ROS (MESH:D017382), docetaxel (MESH:D000077143), cediranib (MESH:C500926), Yoda1 (MESH:C000708435), Ca2+ (-)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** DU145 — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_0105), PC-3 — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_0035), RM11 — Homo sapiens (Human), Melanoma, Cancer cell line (CVCL_W879)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12939218/full.md

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12939218/full.md

## References

192 references — full list in the complete paper: https://tomesphere.com/paper/PMC12939218/full.md

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Source: https://tomesphere.com/paper/PMC12939218