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Life sciences · Journal article
Journal of Experimental & Clinical Cancer Research · August 11, 2026
Raises a question worth testing. It does not answer one.
This is a discovery-phase mechanistic study demonstrating that FAM120A is an interacting partner of EphA2 in progranulin signaling and plays a functional role in bladder cancer cell proliferation, invasion, and xenograft tumorigenesis. The work identifies a putative pathway but remains preclinical; human clinical validation is required before therapeutic or biomarker claims can be substantiated.
In vitro mechanistic study with cell line and xenograft validation. Bladder cancer cell lines and formalin-fixed tissue microarrays; immunocompromised mice for xenograft studies. No human patient cohort enrolled.. Intervention: FAM120A depletion via lentiviral short hairpin RNA (shRNA). Compared with: Control cells with intact FAM120A; progranulin stimulation versus baseline.
FAM120A identified as a novel progranulin-dependent EphA2 interactor through proteomic approaches FAM120A upregulation confirmed in bladder cancer tissues by immunohistochemistry FAM120A depletion via lentiviral shRNA inhibited progranulin-evoked AKT and ERK1/2 activation
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This work provides preclinical evidence that FAM120A may be a therapeutic target in bladder cancer and a potential biomarker, but requires clinical validation through patient cohorts and prospective trials before implementation in practice.
This is a mechanistic, discovery-phase study identifying a novel protein interaction in cancer cell lines and xenografts, without clinical validation or human efficacy data to support therapeutic claims.
As stated by the source record.
This work provides preclinical evidence that FAM120A may be a therapeutic target in bladder cancer and a potential biomarker, but requires clinical validation through patient cohorts and prospective trials before implementation in practice.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
What is missing. This record has no reported figures. That is a gap in the analysis, not a judgement about the study.
Abstract Background Bladder cancer (BC) is one of the most deadly diseases in the USA, with 84,530 new cases and 17,870 estimated deaths in 2026. The growth factor progranulin is involved in several human pathologies, including frontotemporal dementia (FTD), immune response, and cancer. We showed that in BC, progranulin and its signaling receptor, EphA2, drive tumor cell motility, invasion, and in vivo tumor formation, making it a critical pathway in tumor establishment. However, the molecular mechanisms of progranulin/EphA2 action are still poorly defined. Methods Progranulin-dependent EphA2 interactome was explored by proteomic approaches. FAM120A or EphA2 protein levels in BC tissue microarrays (TMAs) and FAM120A protein expression in BC cell lines were analyzed by immunohistochemistry (IHC) and immunoblots, respectively. Progranulin-dependent activation of AKT and ERK1/2 were examined by western immunoblots. EphA2-FAM120A interaction was detected using Co-immunoprecipitation and proximity ligation assays (PLA). In addition, EphA2 and FAM120A colocalization and F-actin cytoskeleton rearrangements were assessed by immunofluorescence. The biological function of FAM120A was determined using lentiviral shRNA approaches, wound healing, motility and invasion, spheroid, soft agar, clonogenic assays, cell cytotoxicity, and in vivo xenograft models. Result We conducted proteomic approaches and identified novel progranulin-dependent EphA2 interactors, including FAM120A, which is a scaffold protein with a putative role in oncogenic pathways. We confirmed that the EphA2 and FAM120A interaction was enhanced upon progranulin stimulation, and FAM120A was upregulated in BC tissues. We further demonstrated that FAM120A was critical for progranulin-evoked AKT and ERK1/2 activation, clonogenic capacity, wound healing, motility, invasion, and 3D spheroid formation of BC cell lines. In addition, FAM120A was essential for anchorage-independent growth and in vivo tumorigenesis in xenograft models. In addition, FAM120A depletion sensitized BC cells to cisplatin treatment. Mechanistically, we showed that FAM120A depletion inhibited progranulin-dependent F-actin cytoskeleton rearrangement through ERK1/2 and RhoA-dependent pathways. Furthermore, we demonstrated that progranulin-induced activation of RhoA was inhibited upon FAM120A depletion. Conclusion The discovery of FAM120A as an oncogenic progranulin-dependent EphA2 interactor provides novel insights into the progranulin/EphA2 signaling axis and uncovers putative novel targets for BC therapy. Furthermore, FAM120A expression may work as a biomarker with diagnostic and possibly prognostic value in BC.
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