SLC34A2 (NaPi2b) Antibodies & Recombinant Proteins for Cancer Research | abinScience

SLC34A2 (NaPi2b) is a sodium-dependent phosphate transporter that plays a critical role in maintaining phosphate balance and regulating pulmonary surfactant production. It is predominantly expressed in epithelial cells of the lungs, intestines, and kidneys, where it supports phosphate reabsorption, nutrient absorption, and respiratory function through its transmembrane transport activity. Structurally, SLC34A2 spans the membrane multiple times, forming a channel-like topology essential for its function.

In recent years, SLC34A2 has garnered attention in cancer biology due to its aberrant expression and mutation across various malignancies, including bladder, ovarian, pancreatic, lung, thyroid, and colorectal cancers. Structural analyses reveal that pathogenic variants—including missense mutations, nonsense mutations, frameshift variants, and in-frame deletions—are distributed across both extracellular loops and transmembrane domains, potentially disrupting phosphate transport or triggering downstream oncogenic signaling. These mutations can impair normal function or confer neomorphic activities, promoting tumor proliferation, invasion, and therapy resistance.

Given its restricted normal tissue expression and upregulation in tumors, SLC34A2 is emerging as a valuable biomarker for cancer diagnosis and prognosis, as well as a targetable molecule in the development of antibody-drug conjugates (ADCs) and other precision oncology strategies.

Role in Cancer: Biomarker and Prognostic Value

In bladder cancer, SLC34A2 is significantly upregulated, correlating with tumor size, stage, and overall survival (p < 0.001, hazard ratio = 1.6, CI: 1.2–2.1). Experimental studies further demonstrate that knockdown or overexpression of SLC34A2 alters tumor cell proliferation in bladder cancer cells, highlighting its functional role in cancer progression [Ye et al., 2017, Cell Death & Disease].

Fig. 1. High SLC34A2 IHC scores correlate with reduced patient survival in bladder cancer cohorts (Kaplan–Meier analysis). [Source: Ye et al., 2017, Cell Death & Disease]

Fig. 2. Knockdown or overexpression of SLC34A2 alters tumor cell proliferation in bladder cancer cells. [Source: Ye et al., 2017, Cell Death & Disease]

A 2021 study by Vlasenkova et al. analyzed >110,000 cancer samples, revealing SLC34A2 as a prognostic indicator across multiple tumor types. Specifically, in ovarian cancer (serous cystadenocarcinoma, n = 299), high SLC34A2 expression reduced median survival to 32 months versus 48 months in low-expression groups (p < 0.0031). In pancreatic cancer (adenocarcinoma, n = 179), the 5-year survival rate dropped to 15% from 28% with high expression (p < 0.0015). Mutations, such as SLC34A2-ROS1 fusions, worsen survival in breast cancer and thymus cancer, while overexpression is linked to poor prognosis in brain cancer, ovarian cancer, and pancreatic cancer [Vlasenkova et al., 2021, Biomolecules].

In non-small cell lung cancer (NSCLC), SLC34A2 overexpression is associated with advanced tumor stages (III-IV) and lymph node metastasis (p < 0.01), reducing 5-year survival to 20% compared to 35% in low-expression groups [Jiang et al., 2016, Tumour Biology]. In papillary thyroid carcinoma, SLC34A2 upregulation correlates with invasion and metastasis via the MAPK signaling pathway, with a hazard ratio of 2.1 for recurrence (p < 0.005) [Huang et al., 2021, Journal of Cancer]. Additionally, in colorectal cancer, high SLC34A2 expression is linked to poor differentiation and shorter disease-free survival (p < 0.01), with a hazard ratio of 1.8 [Ge et al., 2020, Frontiers in Oncology].

Mechanistic Insights: Signaling Pathways

SLC34A2 promotes tumor proliferation via the c-Myc pathway, with knockdown reducing cell viability and tumor burden, reversible by c-Myc restoration. miR-214 suppresses SLC34A2, forming a miR-214–SLC34A2–c-Myc axis. Additionally, SLC34A2 activates Wnt/β-catenin (upregulating Bmi1 in lung cancer stem cells), regulates G2/M via TMPRSS3 in colorectal cancer, and modulates PI3K/AKT (affecting SOX2 in breast cancer stem cells) and Ras/Raf/MEK (suppressing NSCLC tumorigenesis) [Jiang et al., 2016, Tumour Biology; Ge et al., 2020, Frontiers in Oncology]. In thyroid cancer, SLC34A2 enhances MAPK signaling, promoting epithelial-mesenchymal transition (EMT) and metastasis [Huang et al., 2021, Journal of Cancer]. In ovarian cancer, SLC34A2 interacts with EGFR, amplifying downstream ERK signaling and chemoresistance (p < 0.01) [Li et al., 2019, Oncology Reports].

Fig. 3. SLC34A2 knockdown reduces tumor volume in vivo xenograft models. [Source: Jiang et al., 2016, Tumour Biology]

Translational Applications and Antibody Development

SLC34A2’s limited normal tissue expression and its significant tumor elevation establish it as a highly promising therapeutic target in oncology. This selective expression pattern, particularly in malignant tissues, minimizes off-target effects, making SLC34A2 an ideal candidate for targeted therapies. Antibody-drug conjugates (ADCs) such as Rebmab200 and XMT-1536, specifically designed to target SLC34A2, are currently undergoing clinical trials. These ADCs leverage SLC34A2’s overexpression in ovarian cancer and lung cancer, demonstrating potential in improving patient outcomes by delivering cytotoxic agents directly to cancer cells [Moore et al., 2020, Journal of Clinical Oncology; NCT03319628, ClinicalTrials.gov].

Product Application Scenarios

SLC34A2 Research Solutions and Tools

abinScience provides research-grade SLC34A2 research solutions and reagents, mammalian-expressed and validated for cancer research studies. The portfolio includes:

Protein 

Antibody 

Conclusion

SLC34A2 is a high-value target due to its involvement in oncogenic signaling across multiple tumor types. abinScience’s SLC34A2-related protein and antibody products support cancer diagnostics, pathway research, and therapeutic development in bladder cancer, ovarian cancer, and other malignancies.

References

• Vlasenkova, R., et al. (2021). Characterization of SLC34A2 as a Potential Prognostic Marker of Oncological Diseases. Biomolecules, 11(12), 1878.
• Ye, W., et al. (2017). Overexpression of SLC34A2 is an independent prognostic indicator in bladder cancer. Cell Death & Disease, 8(2), e2581.
• Jiang, Z., et al. (2016). The effects and mechanisms of SLC34A2 in tumorigenicity in human non-small cell lung cancer stem cells. Tumour Biology, 37(8), 10383–10392.
• Huang, F., et al. (2021). SLC34A2 Up-regulation And SLC4A4 Down-regulation Correlates With Invasion, Metastasis, And The MAPK Signaling Pathway In Papillary Thyroid Carcinomas. Journal of Cancer, 12(18), 5439–5453.
• Ge, Y., et al. (2020). SLC34A2 promotes cancer proliferation and cell cycle progression by targeting TMPRSS3 in colorectal cancer. Frontiers in Oncology, 10, 585382.
• Li, X., et al. (2019). SLC34A2 promotes ovarian cancer progression via EGFR/ERK signaling pathway. Oncology Reports, 41(5), 2891–2900.
• Moore, K. N., et al. (2020). Safety and activity of the first-in-class NaPi2b-targeting antibody-drug conjugate (ADC) XMT-1536 in platinum-resistant ovarian cancer (PROC): GOG 3043. Journal of Clinical Oncology, 38(15_suppl), 8007.
• ClinicalTrials.gov. (2021). A Study of XMT-1536 in Patients With Cancer (WPA). NCT03319628.

About abinScience

abinScience is a global supplier of premium research reagents, including recombinant proteins, antibodies, assay kits, and custom CRO services tailored for the life sciences. We collaborate with researchers worldwide to support innovation in oncology, immunology, and molecular biology. Our product portfolio is built on scientific precision and a commitment to accelerating translational research.

Our SLC34A2-related protein and antibody products exemplify abinScience’s approach—empowering cancer research with reagents that are rigorously validated and optimized for critical applications such as biomarker discovery and therapeutic development in bladder cancer, ovarian cancer, and more.