




































Berkeley
Pharma Tech
Journal of Medicine

Correspondence: 
hasset1@gmail.com

Keywords:
PTPN
Digestive cancer
Phosphatase
Lung cancer
Tumor promoter

Submitted: May 10, 2023 
Accepted: June 30, 2023 
Published: December 30, 2023

Full Open Access

Creative Commons Attribution 
License 4.0

Abstract
Protein phosphorylation and dephosphorylation are pivotal in regulating protein 
activity. Two key players, protein tyrosine kinases and protein tyrosine phosphatases 
(PTPN), especially non-receptor PTPNs, exert opposing influences in this process. 
While all PTPNs dephosphorylate substrates, their impact on different cancers varies. 
Some act as tumor suppressors in specific cancers, while in others, they may function 
as tumor promoters. This review focuses on comprehending the roles of PTPNs in lung 
and digestive cancers. Notably, lung cancer ranks as the third most common cancer in 
the US, with around 200,000 new cases reported annually. Despite declining rates in 
the United States, stomach cancer remains a major cause of cancer-related deaths 
worldwide. The objective of this review article is to elucidate the functions of PTPN1, 
PTPN2, PTPN3, PTPN6, PTPN11, PTPN12, and PTPN13 in lung and/or digestive 
cancers. Emphasis is placed on exploring their potential as prognostic markers or 
therapeutic targets.

Exploring the Therapeutic 
Potential of PTPN Families in 
Lung and Digestive Cancers
By: Hasset Yishak, Kareem Halwah, and Jiyun Rhim



Berkeley Pharma Tech Journal of Medicine | 83 

1. Introduction 

Cancer is a leading cause of death all over the world, and the complications 
associated with the disease makes it difficult to efficiently treat. Various types 
of cancer exist, such as lung cancer, gastric cancer, breast cancer, lymphoma, 
prostate cancer, and kidney cancer. Lung cancer is the second most common 
cancer in the United States,1 with approximately 80% of lung cancers being non-
small lung cancer (NSCLC). Furthermore, lung cancer accounts for the greatest 
number of deaths stemming from cancer in men with a 5-year survival rate 
ranging from 10 % to 20%.2 Digestive cancer encompasses different types of cancer, 
such as gastric and colorectal cancer. Gastric cancer, also known as stomach 
cancer, significantly affects 1 in 96 men and 1 in 152 women.1 Known as the fifth 
most common cancer in the world, gastric cancer’s 5-year survival rate is 32%.3 
Current cancer treatments include surgery, chemotherapy, hormone therapy, 
radiation therapy, hyperthermia, immunotherapy, and targeted therapy.4,5 
Despite the variety of treatments, these treatments are not fully effective as 
millions of people continuously die from cancer annually. Thus, there is a strong 
drive to develop alternative treatments by exploring the molecular mechanisms 
of various proteins involved in the progression or inhibition of cancer. 

1.1 Introduction to PTPN 

With current experimentation being conducted in regards to novel therapeutics in 
lung and digestive cancer, this review paper explores, as well as summarizes, the 
existing body of scientific literature on the family of protein phosphatases known as 
non-receptor protein tyrosine phosphatases (PTPN). Phosphorylation and 
dephosphorylation are highly used mechanisms by the cell to regulate signaling 
within and between cells. Importantly, PTPNs affect tumor progression by 
dephosphorylating proteins in order to activate or inhibit potentially oncogenic 
pathways.6 This creates a strong potential for PTPN families to be used as a 
prognosis marker and/or therapeutic target in treating lung and digestive tract 
cancers. Therefore, this literature review characterizes the importance of several 
PTPNs, PTPN 1, 3, 6, 11, 12, 13, by summarizing their roles as a tumor promoter, 
tumor suppressor or both as well as exploring their molecular mechanisms in 
digestive and/or lung cancer [Figure 1]. 



Berkeley Pharma Tech Journal of Medicine | 84 

Figure 1: An overview of the role of each PTPN in lung or digestive cancer. PTPNs 
marked in green have tumor suppressing capabilities, red as tumor promoting, and orange as 
having both tumor suppressing and promoting capabilities. 

2. PTPN1

PTP1B, also known as protein tyrosine phosphatase non-receptor 1B, is encoded 
by the PTPN1 gene. Its uncontrolled growth is shown to be correlated with 
growth of digestive cancer, demonstrating PTPN1B’s potential oncogenic role 
in digestive cancer.7 For CRC (colorectal cancer), PTP1B was associated with 
CRC patients’ low overall survival; additional studies also support the 
relationship of PTP1B overexpression and late stage tumors.8 Therefore, 
PTP1B expression level can be utilized as a possible biomarker for prognosis of 
late stage tumors, including CRC.9

2.1 Gastric Cancer 

Likewise, according to the RT-PCR assay, PTP1B was found to be overexpressed 
in gastric cancer tissues relative to normal gastric cells. Amplification of PTP1B was 
associated with poor survival of gastric cancer patients.9 Therefore, the 
amplification of PTP1B can be both used as a biomarker for gastric cancer and 
indicative for poor survival rate, revealing PTP1B’s oncogenic role as a tumor 
promoter in gastric carcinogenesis.10 Furthermore, inhibition of PTP1B in gastric 
cells was associated with hindrance of gastric cancer cell growth in both vitro and 
vivo. Furthermore, its inhibition changed genome-wide expression of genes related 
to cell growth; thus, PTP1B can be directly used as cancer therapy to slow down 
digestive cancer growth.11 

Despite there being evidence of PTP1B functioning as a tumor promoter, 
contrasting ideas in the literature suggest it can also function as a tumor suppressor 
depending on the cellular context.12 For example, when EGF (Epidermal Growth 
Factor) binds to its receptor EGFR, it activates the Shc-Grb2-SOS interaction. At 
the end of interaction, Ras activates MEK/Erk pathway’s Raf and ends with Erk 



Berkeley Pharma Tech Journal of Medicine | 85 

entering the nucleus to activate FGF2 (Fibroblast Growth Factor 2) which causes 
uncontrolled growth of the cancer.13 If PTP1B does not interfere in the process, 
FGF2 promotes cancer growth. However, PTP1B can inhibit the process by 
interacting at the beginning or end of the Shc pathway and/or prohibiting the entry 
of Erk into the nucleus PTP1B’s inhibition of signaling pathways leads to decrease 
in cancer growth13 [Figure 2]. 

Figure 2: Effect of PTP1B on the pathway of cancer growth. When PTP1B prohibits 
Shc-Grb2-SOS interaction, the growth of cancer is prohibited due to a decreased expression of 
FGF2. Oppositely, when PTP1B does not stop the pathway, the cancer cells will be able to 
proliferate and duplicate itself. 

2.2 Non-Small Cell Lung Cancer (NSCLC)

In regards to NSCLC, PTP1B levels increase with the progression of the cancer, 
highlighting how increased PTP1B levels are associated with poor survival of 
patients with NSCLC.14 Additionally, when PTP1B expression was downregulated, 



Berkeley Pharma Tech Journal of Medicine | 86 

there was a decrease in cell proliferation and metastasis in vitro. Likewise, 
downregulation of PTP1B in mice transfected with NSCLC cells showed a 
significant decrease in tumor size compared to control mice that had unaltered 
PTP1B levels. These results provide evidence for PTP1B’s role as a tumor promoter 
in lung cancer. Mechanistically, PTP1B activates the oncogene, Src (Proto-
Oncogene c-Src), which promotes NSCLC proliferation and metastasis. Therefore, 
designing an inhibitor of PTP1B could be promising in treating NSCLC due to its 
suggested tumor suppressing capabilities.14 

In Lung Adenocarcinoma (LUAD), PTPN1 is downregulated according to 
comprehensive bioinformatics analysis. Its upregulation has been conferred with 
overall higher survival rates in patients, demonstrating the overexpression of 
PTPN1 as a potential therapeutic target for treating LUAD patients. As well, 
decreased expression can be a prognostic biomarker for lung cancer progression.15 

3. PTPN2 

In CRC tumor cells, PTPN2 levels are enhanced, with greater PTPN2 gene 
expression correlated with reduced T cell activity, recruitment, and cytotoxicity.16 It 
is also inversely correlated with low immune checkpoint molecule expression.16 
PTPN2 negatively regulates IFN-γ signaling, a pathway involved in the 
upregulation of immunity related genes, by dephosphorylating proteins involved in 
the signaling pathway. Mouse models with tumors deficient in PTPN2 had 
increased activation of the IFN-γ receptors by the cytokine, IFN- γ, which resulted 
in the phosphorylation of the signal transducer and transcription protein, STAT1 
[Figure 3]. STAT1 is able to homodimerize and enter the nucleus to drive 
transcription of genes involved in immunity related processes such as MHC-1, 
possibly PD-1, and others [16-8]. This results in the activation of CD4+ Th1 cells 
and increases the cytotoxicity of CD8+ T cells, which inhibits the growth of the 
tumor.16 CD4+ Th1 cells is a type of T helper cell that releases cytokines in response 
to inflammation and is also involved in the activation and growth of CD8+ T cells, 
otherwise known as killer T-cells. Therefore, tumors deficient in PTPN2 have 
increased IFN-γ signaling, which results in a significant reduction of tumor size as 
well as greater mRNA expression of chemokines, like cxcl9/10/11 and ccl5.16 This 
suggests that the inhibition of PTPN2 through a small molecule might prove to be 
an effective potential therapeutic drug. While additional experimentation would 
need to be conducted to better understand the kinetics involved with the inhibitors, 
a recent paper by Zhu et al.19 has identified various small noncytotoxic molecule 
inhibitors that were able to inhibit PTPN2. This resulted in successful upregulation 



Berkeley Pharma Tech Journal of Medicine | 87 

of genes involved in IFN-γ signaling, and the sensitization of the CRC tumor to 
treatment. 

3.1 KRAS Gene 

Approximately 40% of patients with CRC have a missense mutation in the KRAS 
(Kirsten rat sarcoma viral oncogene homologue) gene.20 Those with the mutation in 
the KRAS gene tend to have a relatively poorer prognosis compared to CRC 
patients with wild type KRAS.20 KRAS encodes for the protein K-ras, which is part 
of the signaling pathway of RAS/MAPK, a pathway that induces cellular 
proliferation, migration, and cell growth. Mutations in KRAS are thought to be the 
most common oncogenic gene driver in human cancer, especially in pancreatic 
cancer, CRC, and NSCLC.21 These mutations lead to a continued active state of 
KRAS that result in continuous proliferation of tumor cells by upregulating the 
RAS/MAPK pathway. PTPN2 has been identified as a key regulator of KRAS due 
to its ability to dephosphorylate KRAS, activating the KRAS-mediated MAPK 
pathway.22 Therefore, it is hypothesized that inhibition of PTPN2 could suppress 
cancer by no longer activating KRAS, presenting itself to be a novel therapeutic 
target.22 

Figure 3: IFN-γ signaling pathway in PTPN2 deficient tumor cell. STAT1 remains 
phosphorylated and homodimerizes in order to enter the nucleus and induce the transcription 
of immune related genes. This ultimately leads to an increase in chemokines as well as CD8+ 
cells that reduce the size of the tumor. 



Berkeley Pharma Tech Journal of Medicine | 88 

4. PTPN3

Nonsense and frameshift mutations in PTPN3 that hinder its phosphatase activity 
have been found in lung cancer tissue.23 Consequently, overexpression of PTPN3 
results in reduced lung cancer cell growth and migration, indicating that it might 
have tumor suppressor capabilities.24,25 PTPN3 is capable of suppressing lung cancer 
cell invasion by dephosphorylating the protein, Src, at Tyr416, which inhibits Src-
mediated phosphorylation of Tyr652 on another protein known as Dishevelled 
Associated Activator of Morphogenesis 1 (DAAM1).24 Tyrosine phosphorylation 
of DAAM 1 at Tyr652 by Src is needed for DAAM1 dimerization.24 In the absence 
of PTPN3, DAAM1 is able to dimerize, leading to long and thick actin, which 
improves cancer cell migration. PTPN3 knockdown cells moved 30% faster than the 
control which had normal expression of PTPN3.24 

4.1 EGFR 

Additionally, PTPN3 is able to target EGFR for lysosomal degradation inhibiting 
proliferation of cancer cells. PTPN3 is capable of dephosphorylating EPS 15, which 
promotes the endocytosis of EGFR, given that EGFR is bound to its ligand, EGF.25 
When EGFR is internalized via lipid raft-mediated endocytosis, it is either recycled 
back to the cell surface, targeted to the lysosome for degradation, or internalized to 
subcellular compartments.25 Thus, since PTPN3 is capable of causing EGFR to be 
degraded via its effects on Eps 15, PTPN3 functions as a tumor suppressor. 
Overexpression of PTPN3 resulted in a decrease of EGFR levels when stimulated 
by EGF.25 This confirmed dephosphorylation of Eps15 by PTPN3 is capable of 
suppressing tumor growth. 

5. PTPN6 

5.1 CRC Tissue 

PTPN6 was highly expressed in CRC tissue as demonstrated by qPCR, CCK-8, 
clone formation assay, and other assessments.26 The overexpression of PTPN6 in 
malignant colon cancer cells was associated with poor prognosis in colon cancer 
patients. Conversely, the inhibition of PTPN6 restrained migration, invasion, and 
clonogenics of CRC tissues.26 Therefore, PTPN6 amplification can potentially be 
used as a biomarker for CRC and its progression. PTPN 6 is a possible tumor 
promoter due to its ability to promote proliferation and migration of tumor cells. 
Additionally, PTPN6 interacts with EGFR, a receptor known to induce pathways 



Berkeley Pharma Tech Journal of Medicine | 89 

involved in proliferation, migration, and adhesion. Increased expression of both 
PTPN6 and EGFR resulted in the greatest cancerous proliferation as compared to 
cells with only PTPN6 or EGFR overexpressed. Thus, either targeting PTPN6 or 
the PTPN6-EGFR complex with an inhibitor could be a potential therapeutic. 

However, other research suggests PTPN6 might have tumor suppressing 
capabilities by decreasing the levels of the protein SP1 (Specificity Protein 1). 
MAPK pathway is typically activated by SP1; however, due to PTPN6’s inhibition 
of SP1, MAPK pathway is consequently suppressed. PTPN6 inhibition promotes 
enhanced chemosensitivity within CRC cells. Yet, more research needs to be 
conducted in order to further understand the various effects of PTPN6 within 
CRC.27

6. PTPN11

6.1 Shp2 

PTPN11 is a gene that encodes for Shp2, a protein consisting of two N-terminal Src 
homology (SH2) domains, a catalytic PTP domain, and a C- terminal tail with 
tyrosyl phosphorylation sites.28 Shp2/PTPN11 is involved in promoting signaling 
pathways such as Ras/ERK, RAS/MAPK, JAK/STAT, as well as KRAS signaling 
within the tumor microenvironment.28 Increased expression of Shp2/PTPN11 is 
associated with a 5.34 fold increase in risk for gastric cancer and a 2.95 fold increase 
in risk for lung cancer.29 Furthermore, other studies have found Shp2 to be highly 
expressed in 60.78% of gastric cancer and 70% of NSCLC tissue samples.29 

Patients infected with Helicobacter pylori are at a greater risk for gastric cancer.30 A 
virulence factor of H. pylori known as Cytotoxin associated antigen (CagA) is able 
to interact with the epithelial gastric cells, leading to the Src-dependent tyrosine 
phosphorylation of CagA.30 The phosphorylated CagA binds with Shp2, forming a 
complex that allows for the transition of Shp2 into its active form. In its active form, 
Shp2 is capable of inducing oncogenic properties, such as neoplasia, gastric atrophy, 
and increased migration of gastric epithelial cells.30 In contrast, in many cases of lung 
cancer, a missense mutation in the PTPN11 gene leads to a dysfunctional Shp2 
protein that results in inappropriate activation of various signal transduction 
pathways.31 

Due to the proto-oncogenic nature of PTPN11, various strides have been made in 
developing small molecule inhibitors which are capable of binding to the catalytic 
site of Shp2. One potential inhibitor, SHP099, is able to bind to the N-terminal, C-



Berkeley Pharma Tech Journal of Medicine | 90 

terminal and PTP domain on SHP2, resulting in increased immune system activity 
such as greater IFN-γ  signaling. This induced greater transcription of cytotoxic T-
cell related genes within a mice model for lung cancer treatment.31 While most of 
Shp2 inhibitors are in the preclinical study stages, the potential of PTPN11 as a 
therapeutic drug target is a promising prospect in treating many types of cancers, 
including gastric and lung cancer. 

7. PTPN12 

PTPN12 is a tumor suppressor that normally has an inhibitory effect on the 
Ras/MEK/ERK signaling by dephosphorylating the protein Shc.32 However, it was 
hypothesized that a missense mutation in PTPN12 would leave Shc 
phosphorylated, resulting in hallmarks of cancer, such as cellular proliferation and 
increased migration.33 For example, researchers identified that a variant of PTPN12 
(rs3750050 G allele) increased the risk of CRC by 19%.33 

Conversely, upregulation of PTPN12 has been correlated with incidences of 
esophageal carcinoma, stomach adenocarcinoma and colorectal cancer, making it a 
highly favorable candidate for biomarker.34 The researchers acknowledge that these 
findings are seemingly in contradiction with previous literature that suggests 
PTPN12 to have tumor suppressing capabilities.34 Another study showed that 
PTPN12 might be a favorable prognosis marker for NSCLC in patients due to 
higher expression levels associated with higher 5-year survival rates, especially within 
the subgroup with non-squamous cell carcinoma.35 Due to the non-definitive role 
of PTPN12, further research still needs to be conducted.33-35 

8. PTPN13

Like many of the other PTPNs previously discussed, PTPN13 has been shown to 
have both tumor suppressive and tumor promoting roles depending on the cancer 
being examined.36 PTPN13 was shown to act as a tumor suppressor in breast 
cancer37 and high grade serous ovarian carcinoma.38 Likewise, in lung cancer, 
PTPN13 has been shown to have tumor suppressor capabilities by acting on various 
pathways.38-42 

PTPN13 is downregulated in lung cancer mainly due to a loss of at least one copy 
of the PTPN13 locus at chromosome 4q.40 40% of cases are not accounted for by 
this mechanism, however, and further research is needed to understand how it is 
downregulated in those cases.40 Various studies have shown that PTPN13 



Berkeley Pharma Tech Journal of Medicine | 91 

downregulation results in increased proliferation of NSCLC [39-41] in addition to 
greater tumor cell size.40 To further confirm the role of PTPN13, PTPN13 
expression was restored to PTPN13 knockdown cells and this resulted in slower 
proliferation of NSCLC.40 

PTPN13’s tumor suppressing capabilities stem from it inhibiting various oncogenic 
pathways. This is explored through the use of microRNAs which are known to have 
different effects on LUAD proliferation. For example, miR-36143 and miR-34044 
inhibit LUAD cell growth while miR-48345 and miR-22446 promote LUAD cell 
growth. MicroRNA-30e-5p (miR-30e) is of interest to this review paper due to its 
ability to downregulate PTPN13 [Figure 4B]. Knockdown of miR-30e suppresses 
LUAD growth, suggesting that the presence of miR-30e is indicative of poor 
prognosis.39 Upregulation of PTPN13 counteracts the tumor promoting effects of 
miR-30e by inhibiting EGFR/AKT signaling.39 

PTPN13 was also shown to inhibit the Src/ERK/YAP1 signaling pathway, further 
contributing to its tumor suppressive properties in lung cancer. YAP1 promotes the 
proliferation of NSCLC cells, classifying it as an oncoprotein.42,47 YAP1 has also 
been shown to activate the MEK/ERK pathway by promoting the expression of 
FGF239 [Figure 4A]. Nuclear YAP1 levels were increased in PTPN13 knockdown 
cells, indicating that PTPN13 might act to inhibit YAP1. It is also thought that 
YAP1 could be upregulated via the MEK/ERK pathway when PTPN13 is 
suppressed.42 Thus, another pathway by which PTPN13 acts as a tumor suppressor 
is by inhibiting the MEK/ERK pathway, which suppresses the upregulation of 
YAP1. 

Various cancers, including lung cancer, have been shown to have higher than 
normal levels of HER2, indicating that upregulation of HER2 leads to tumor 
growth and poor prognosis. PTPN13 downregulates HER2 activity by 
dephosphorylating the cytoplasmic domain of HER2, possibly decreasing the 
metastasis associated with HER2-overactive NSCLC tumor cells.41 PTPN13 was 
also found to dephosphorylate EGFR.40 Downregulation of PTPN13 increased 
EGF-stimulated EGFR and HER2 phosphorylation, leading to increased activation 
of MAPK and Akt dependent pathways.40 



Berkeley Pharma Tech Journal of Medicine | 92 

Figure 4: Overview of PTPN13’s effect on various pathways. PTPN13 has been 
shown to work by affecting the MEK/ERK pathway in different ways. A) PTPN13 can 
downregulate EGFR and HER2 receptors by dephosphorylating them [40]. YAP1 levels 
decrease in the presence of PTPN13, which could be due to PTPN13 inhibiting the MEK/
ERK pathway. B) miR-30e is capable of downregulating PTPN13, resulting in increased cell 
growth in LUAD by promoting EGFR/AKT signaling. 

9. Current Clinical Trials

There are ongoing clinical trials exploring the efficacy of small molecule inhibitors 
on PTPN11, like JAB-3068 and JAB-3312, in patients with advanced solid tumors. 
It is hypothesized that these small molecules will prevent various oncogenic 
phenotypes associated with hyperactivation of Shp2 mediated signal transduction 
pathways. JAB-3068 is currently in Phase 1/2a and is recruiting patients with 
advanced solid tumors of NSCLC, head and neck cancer, esophageal cancer, and 
other metastatic solid tumors.49 The experiment will consist of oral administration 
of JAB-3068 every morning after a six hour fast.49 A pharmacokinetics (PK) analysis 
will be taken which will be used to monitor the drug as it reacts with the body. 
Similarly, the small molecule inhibitor JAB-3312 is in Phase 1 Study and is also 
recruiting patients with advanced solid tumors of NSCLC, CRC, pancreatic ductal 
carcinoma, esophageal squamous cell carcinoma, head and neck squamous cell 
carcinoma, breast cancer, and other solid tumors. The experiment will consist of 
daily oral administration of the drug in treatment cycles of 21 days.50 

9.1 Matched Targeted Therapy 

Another ongoing clinical trial is utilizing Matched Targeted Therapy (MTT) in 
order to test the efficacy of Trametinib on PTPN11 and other proteins involved in 



Berkeley Pharma Tech Journal of Medicine | 93 

cancer progression. Specifically, Trametinib is a kinase inhibitor that blocks the 
abnormal protein signals that cause cancer cell multiplication. The drug will be 
consumed orally with two mg per day. The trials are expected to be completed by 
2026. Some measures that researchers will be noting are short-term and long-term 
progression, duration of response, survival, adverse effects, and more.51 

10. Future Directions & Conclusion 

This article provided a review of various PTPN protein families in regards to lung 
and digestive cancer with the goal of providing researchers foundational 
information in their efforts to develop therapeutics that target PTPNs. Many 
studies have investigated the roles of PTPNs in tumor progression, outlining how 
PTPNs act on different pathways and thus affect tumor progression differently. 
This review paper focuses on the molecular mechanisms that underlie the effects of 
PTPNs, as it could aid in determining if PTPN therapeutics are worth exploring. 
Many of these PTPNs can be used as biomarkers and/or prognosis markers as 
overexpression or underexpression of certain PTPNs are associated with each cancer 
[Figure 5]. In regards to digestive cancer, PTPN2 and PTPN11 were shown to have 
tumor promoting capabilities while PTP1B, PTPN6, and PTPN12 were shown to 
have both tumor promoting and tumor suppressing capabilities. In lung cancer, 
PTPN3, PTPN12, and PTPN13 were shown to have tumor suppressing 
capabilities while PTPN11 had tumor promoting capabilities. PTP1B was seen to 
have both tumor suppressing and tumor promoting capabilities depending on the 
cellular substrate. 

Given these PTPNs and their varying effects on each cancer, therapeutic targets that 
act to either promote or suppress various PTPN have great potential for cancer 
treatment. To suppress PTPNs with tumor promoting capabilities, researchers 
could look into developing inhibitors that bind to the PTPN proteins. In contrast, 
in order to promote PTPNs with tumor suppressing capabilities, researchers could 
look at developing transcription factors that enhance PTPN gene expression. 
Therefore, additional clinical trials and research need to be conducted in order to 
better understand how to mechanistically target PTPNs to develop effective 
treatments for lung and digestive cancer. 



Berkeley Pharma Tech Journal of Medicine | 94 

PTPN Member Lung Cancer Digestive Cancer 

PTPN1/PTP1B Biomarker: Increased levels of PTP1B 
in NSCLC; decreased levels of PTPN1 

in LUAD 

Therapeutic: Inhibition of PTP1B in 
NSCLC 

Biomarker: Increased levels of 
PTP1B in CRC, gastric cancer 

Therapeutic: Inhibition of PTP1B 
blocks Shc-Grb2-SOS pathway and 

MEK/Erk pathway 

Contrasting: Tumor suppressor 
qualities based on cellular context 

PTPN2 

Insufficient Research 

Biomarker: Increased levels of 
PTPN2 across all stages of CRC 

Therapeutic: Inhibition of PTPN2 
which could increase IFN-γ signaling 

pathway and suppress KRAS-
mediated MAPK pathway 

PTPN3 Biomarker: Decreased levels of 
PTPN3 in lung cancer tissue 

Therapeutic: Upregulation of PTPN3 
to allow for the dephosphorylation of 

Src and targeting of EGFR for lysosomal 
degradation 

Insufficient Research 

PTPN6 

Insufficient Research 

Biomarker: Increased levels of 
PTPN6 in CRC 

Therapeutic: Inhibition of PTPN6-
SP1-MAPK pathway to increase 
chemosensitivity of tumor cells; 

Inhibition of PTPN6-EGFR complex 



Berkeley Pharma Tech Journal of Medicine | 95 

PTPN11 Biomarker: Increased levels of 
PTPN11/Shp2 in 70% of NSCLC tissue 

samples 

Therapeutic: Small molecule inhibition 
of PTPN11/Shp2 which prevents Shp2 
mediated signal transduction pathways 

that are hyperactivated 

Biomarker: Increased levels of 
PTPN11/Shp2 in 60.78% of gastric 

cancers 

Therapeutic: Small molecule 
inhibition of PTPN11/Shp2 which 

prevents Shp2 mediated signal 
transduction pathways that are 

hyperactivated 

PTPN12 Prognosis Marker: Increased levels of 
PTPN12 are associated with higher 5-

year survival rates in NSCLC 

Biomarker: Increased levels of 
PTPN12 are correlated with 

incidences of digestive cancers 

Contrasting: Other research has 
shown PTPN12 as a tumor 

suppressor that normally has an 
inhibitory effect on the 

Ras/MEK/ERK signaling by 
dephosphorylating the protein Shc 

PTPN13 Biomarker: Decreased levels in 
NSCLC 

Therapeutic: Upregulation of 
PTPN13 to inhibit the Src/ERK/YAP1 
signaling pathway, counteract the effects 
of miR-30e, and to downregulate HER2 

activity 

Insufficient Research 

Figure 5: Summary of PTPN families and their potential as a biomarker, prognosis marker, and or/ therapeutic 
target in lung and digestive cancer. Green represents PTPN as a tumor suppressor. Red represents tumor promoter. 
Orange represents both tumor suppressor and promoter capabilities. “Contrasting” refers to conflicting research regarding the 
role of the PTPN. “Insufficient Research” refers to not enough publications on the topic to include in the review. 



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